Home About Us Contact Us

Official Journals By StatPerson Publication

Table of Content-Volume 12 Issue 2 - November 2019


 

 

Histomorphological spectrum of oral squamous cell carcinoma in a tertiary care centre: A four-year study

 

Rajeswari Thivya Dhanabalan1*, Chitra Thukkaram2, Shifa Syed Ibrahim3

 

1Assistant professor, Department of Pathology , Chettinad Hospital and Research Institute

2Professor, Department of Pathology , Karpaga Vinayaga Institute Of Medical Sciences

3Assistant professor, Department of Pathology , Madurai Government Medical College

Email: drrthivya@gmail.com, drchitrathukkaram@gmail.com , shifafrin@gmail.com

 

Abstract               Background: Oral cancer is a global health problem. Among oral cancers squamous cell carcinoma is the predominant malignancy. In this study we have attempted to evaluate the prognostic factors of oral squamous cell carcinoma based on histomorphological parameters. Study Design: Cross sectional observational study. Aim: 1. To grade Squamous cell carcinoma 2. To evaluate the histopathological and clinical prognostic factors Methods: The present study was conducted in the Pathology department, , Karpaga Vinayaga Institute Of Medical Sciences, Maduranthagam, Tamil Nadu over a period of 4-years from September 2012 to September 2016. Sixty four cases were included in our study. Data - such as age, sex, site of lesion, histopathological type of tumor, margin and lymph node status were collected and analyzed. Results: Out of 64 cases well differentiated squamous carcinoma was the most common malignancy. Most of the cases fall in 51-60 age group. Male: female ratio is 1.28. Most of the cases were located in buccal mucosa (60.93%) having an ulceroproliferative pattern of growth (31.25%) and the greatest diameter was of 2-4 cm (53.12%). 39.06% cases showed lymphnode metastases. Microscopically margin invasion was noted in 32.81% cases. Conclusion: From this study we conclude Squmous cell carcinoma well differentiated grade is more prevalent in this region. Histopathological parameters like tumour size, extracapsular extension in nodes and nodal deposits are the most significant prognostic factors for further management. Histological grading along with the deep invasive border involvement pattern also influences the outcome of the disease.

Key Words: Oral squamous cell carcinoma, grading, lymphnode metastasis, prognosis

 

 

INTRODUCTION

Globally oral cancer is a serious health problem with increasing morbidity and mortality rates. Annually 3,00,000 patients are reported to suffer from oral cancer all over the world, of which more than 60% are from developing countries.1 In India oral cancer is a leading health problem affecting up to 42% of the males and 18 % of the females.2,3 It is the commonest malignancy in males and third most common in females with an incidence rate of 12.8% and 7.5% respectively 4, 5.In the oral cavity, squamous cell carcinoma (SCC) is the most prevalent malignant neoplasm, hence it is frequently referred as “oral cancer”. Other neoplasms of the oral cavity include adenocarcinoma, malignant melanomas, odentogenic tumors, bone tumors, salivary gland tumours and secondary deposits 6, 7. Squamous carcinoma is a highly aggressive malignant neoplasia. The prognosis of oral cancers varies significantly with respect to age, site, tumor size,histopathological grading,tumor margins and lymphovascular invasion. Recently numerous prognostic variables related to oral SCC are described, some of them related to the patient activities and others inherent with the molecular profile of the epithelial cells. But the overall prognosis is poor with the survival rate less than 50% 8.The purpose of this study is to evaluate the prognostic factors of oral cancer and it is mainly focused on its histopathological parameters.

 

MATERIALS AND METHODS

This study includes the analysis of malignant oral tumors received in the histopathology section in the Department of Pathology, Karpaga Vinayaga Institute of Medical Sciences, Maduranthagam, Tamil Nadu over a period of four years from September 2012 to September 2016. It is a cross sectional study, both retrospective (Sep 2012 to Sep 2015) and prospective (Sep 2015 to Sep 2016). Altogether 64 specimens were included in the study. Data such as age, sex, site of lesion, histopathological type of tumor, margin and lymph node status were collected and analyzed.

Inclusion criteria

Excised specimens of all primary oral squamous cell carcinoma patients including mandibulectomy (radical, segmental), maxillectomy, glossectomy and hemiglossectomy, irrespective of age and gender that were sent to our department from September 2012 to September 2016 were included. Retrospective cases that were included were ensured to have a complete clinico-pathological data and a complete set of paraffin blocks available.

Exclusion criteria

Patients on radiotherapy or chemotherapy, incomplete clinicopathological data, bone tumors of maxilla and mandible, odontogenic tumours, salivary gland tumours, secondaries and incisional biopsies were excluded. For the analysis of retrospective cases, data was retrieved from the records and the slides were retrieved and reviewed. The specimens [prospective period] were received in 10% formalin. Gross examination of surgical specimens was performed and recorded. Adequate representative tissue sections from the lesions were taken. The material was processed under standardized conditions for paraffin embedding and sections of 4µ thickness were taken. The sections were stained with haematoxylin and eosin (HandE) and then the slides were interpreted. Grading was done by Broder system and staging was done by TNM staging.

RESULTS

The total number of cases received in our department during the study period was 7732. Out of this 527 cases belonged to oral faciomaxillary surgery department and 64 cases which satisfied the above criteria were included in this study. Out of the 64 cases, 36 were male(56.25%) and 28 were female (43.75%). Male: female ratio was 1.28[Table1]. In males most cases were seen a decade earlier [41-50 age groups]. In females most cases were noticed in 51-60 age groups. Majority of the cases were in 51-60 age groups. Mean age was 53.95 years [Table 1]


 

Table 1: Histopathological spectrum, age and sex wise distribution of oral malignancies

Spectrum of malignancy

31-40

41-50

51-60

61-70

71-80

Total

M

F

M

F

M

F

M

F

M

F

M

F

SD

0

0

0

0

0

0

1

1

0

0

1

1

VERRUCOUS

0

1

0

0

2

1

1

1

1

0

4

3

SCCWD

6

0

6

4

8

7

4

3

1

1

25

15

SCCM D

1

0

3

4

0

1

0

3

0

0

4

8

SCC PD

0

0

2

0

0

1

0

0

0

0

2

1

Total

7

1

11

8

10

11

6

7

2

1

36

28

Percent

10.93

1.56

17.18

12.5

15.62

17.18

9.37

10.93

3.12

1.56

56.25

43.75

Buccal mucosa (60.93%)[Fig 1] was the most commonly involved site, followed by tongue (12.5%)[Fig 2] and alveolus (10.93%). The least commonly involved site was hard palate (1.56%)[Table2].Based on the gross appearance, the tumours were subdivided as ulcerative, ulceroproliferative, proliferative and infiltrativein this study. Majority of the cases in our study were ulceroproliferative (31.25%) and infiltrative (26.56%). In the cases reported as SD, one case presented as an ulcer and other case as a leukoplakic patch. Most of the VC cases were either ulceroproliferative or proliferative, SCCWD cases were ulceroproliferative, SCCMD were either ulcerative or ulceroproliferative and SCCPD cases were ulcerative, ulceroproliferative and proliferative each. [Table3].The most common case seen during our study period was well differentiated squamous cell carcinoma (SCCWD) [Fig 3] constituting around 62.5%, followed by moderately differentiated squamous cell carcinoma (SCCMD) [Fig 4] constituting 18.75%, then comes verrucous carcinoma (VC) forming 10.93% [Fig 5], next was poorly differentiated squamous cell carcinoma (SCCPD) 4.68% and finally severe dysplasia (SD) constitute around 3.125% [Fig 6] [Table1]. Most tumours [34 cases] were of size2-4 cm (53.12%) and it comes under T2 of TNM staging. Twelve cases (18.75%) were less than 2 cm in size (T1) and 12 cases (18.75%) were more than 4 cm in size (T3) and 6 cases (9.37%) were more than 4cm with underlying bone invasion [Table 4].

 

1 

Table 3: Gross appearances of oral malignancies

Spectrum of malignancy

Ulcerative

UlceroProliferative

Proliferative

Infiltrative

Patch

SD

1

0

0

0

1

VERRUCOUS

1

2

3

1

0

SCCWD

9

14

5

12

0

SCCM D

4

3

1

4

0

SCC PD

1

1

1

0

0

Total

16

20

10

17

1

Percent

25%

31.25%

15.63%

26.56%

1.56%

Fig 1: Hemimandibulectomy specimen showing infiltrative growth, involving the buccal mucosa and the inset showing cut surface of the growth

23 

Figure 2: Glossectomy specimen showing ulceroproliferative growth

Grossly in all the cases we had studied, margins were free. Microscopically the margins were involved in 21 cases (32.81%). MDSCC show marginal involvement in 50% of the cases [Table 5]. 25 cases showed lymphnode metastases. SCCPD (66%) was the most common tumor with lymphnode metastases, followed by well differentiated SCC (45%) and moderately differentiated SCC (41%). Verrucous carcinoma and severe dysplasia cases did not show any nodal metastases. Out of the nodal metastasing cases, 12 cases showed single ipsilateral nodal involvement (N1) and 13 cases showed multiple ipsilateral nodal involvements (N2). None of the cases included in our study showed contralateral nodal involvement or size more than 3 cm. [Table 6]

Table 5: Margin involvements

Spectrum of malignancy

Involved cases

Uninvolved cases

Total

SD

0

2

2

VERRUCOUS

1

6

7

SCCWD

13

27

40

SCCM D

6

6

12

SCC PD

1

2

3

Total

21

43

64

Percent

32.81

67.19

100

Table 6: Lymphnode metastases

Spectrum of malignancy

Involved

Uninvolved

Single

Ipsilateral

<3cm

Multiple

Ipsilateral

Or 3-6 cm

Contralateral

>6cm

Total

SD

0

0

0

0

2

VERRUCOUS

0

0

0

0

7

SCCWD

11

7

0

18

22

SCCM D

1

4

0

5

7

SCC PD

0

2

0

2

1

Total

12

13

0

25

39

Percent

18.75

20.31

 

39.06

60.94

DISCUSSION

Oral cancer is a universal health problem. Nearly 3 lakh new cases are detected every year, among them more than 60% occur in developing countries. Our Indian subcontinent has a share of one third of these cases. Oral cavity stretches from lips to palatoglossal folds. Oral cavity proper is the space between teeth and gingiva. It is superiorly bounded by hard palate and inferiorly by tongue and floor of tongue. Oral SCC is due to increased and disorganized proliferation of the oral epithelium. It is defined as an invasive epithelial neoplasm having varying degrees of squamous differentiation with a tendency for early and widespread lymph node metastases, developing commonly in individuals with habit of alcohol and tobacco-consumption in their 5th and 6th decades of life. Its ICD-O code is 8070/3.9 Due to its rich blood supply and lymphatic drainage the chance of nodal metastasis is comparatively high in oral SCC thereby making it as a grave disease. Moreover, its increasing incidence rate, poor survival rate, functional and cosmetic defects it leaves has gained it immense importance, necessitating early diagnosis and treatment. Even though oral cavity is easily accessible for complete examination, due to ignorance or inaccessibility to health care, often oral cancer are detected at its later stages. Our knowledge on etiology and pathogenesis of oral cancer has improved due to the development of molecular genetics. According to Bundgaard et al, in the era of molecular genetics, the role of clinical and histopathological parameters of prognostic significance in selection of patients for treatment remains uncertain 10. In this study we have tried to emphasize the clinical and histopathological factors influencing the outcome of SCC patients. In this study SCCWD (62.5%) was the most common malignancy. Similar to our study most of the studies also showed SCCWD as the most predominant malignancy, but the percentage was slightly lower in their studies than in our study.8,11,12 But in Ahmad khan et al study SCCMD was the most predominant and there were no reported cases of SCCPD.13 In addition, in our study VC and SD were also detected. Detection of this early and pre invasive carcinoma in our study suggest an increased awareness among the common people and their early medical assistance seeking behavior in our area.

4

            Figure 3                                    Figure 4                                                            Figure 5                                     Figure 6

Figure 3: HandE showing SCCWD (10X) and inset showing keratin pearl (40X); Figure 4: HandE showing SCCMD (10X) and inset SCCMD (40X); Figure 5: HandE showing VC with pushing margins; Figure 6: HandE showing SD (10X) and inset SD (40X)

 

The analyzed SCC cases were in the age group 31 to 80 yrs. The youngest was 31year and the eldest was 77 year old. SCC was more commonly seen in 41-50 year group and it was comparable to Kiran et al, Khaleel et al and Saadia Akram et al studies.14,15,16 But in Dragomir et al and Smitha S and Alka’s studies the incidence was in slightly older age group 60-69years and in Mirza et al study peak incidence were in 51-60 years17,18,19. In western set up, the peak incidence is 60-70 years while in Asia it occurs generally earlier at about 50-60 years. This reflects the differences in their culture and habits. In this study it was even a decade earlier. Incidence of this tumour in young age group in Asia is attributed due to their massive tobacco chewing habit and unhealthy oral hygiene. But in Western countries, nowadays there is a rise in the incidence of oral SCC in the younger age group due to HPV infection as a result of their promiscuous sexual habits.20 The mean age in our study group was 53.95 years and it was slightly higher than Deepa V Babji et al study which was 47.96 years and lower than that of Ahmad khan et al studies which was 64.65years.13,21 In our study males outnumbered females and the ratio was 1.28 which was on par with many studies13,14,15 But in Dragomir et al study 90% of cases were seen in males 17. Predominance of male incidence is commonly seen in Southeast Asian studies. Recently there is a rise in female oral SCC patients which can be attributable to our changing culture and life style. Tumours can arise anywhere in the oral cavity. The sites vary geographically depending on the risk factors. The commonest sites involved by the oral malignancies include buccal mucosa, gingiva, hard palate, tongue and the floor of mouth9.In our study most commonly involved site was buccal mucosa and it was similar to other studies 14,15,16,20 In the studies among the Asian populations, oral SCC was commonly reported in buccal mucosa because of their betel quid/tobacco chewing habits.22 But in Dragomir et al study tongue was the most common site.17 Regarding gross appearance most of the cases showed ulceroproliferative growth (31.25%). But in Dragomir et al study ulcerative pattern was the most common presentation.17 Different histologic grading systems such as Broder’s, Anneroth’s, Bryne’s and Jakobsson’s are available but we used Broder’s grading.23 Under Broders grading system tumours are traditionally graded into well, moderately-, and poorly differentiated SCC based on the degree of keratinisation, cellular and nuclear pleomorphism and mitotic activity.9 In our study about two third of the cases belonged to well differentiated SCC (62%). This was comparable with other studies in the literatures.6,14,15,16,24 Dragomir et al study also showed well differentiated SCC as predominant grade but at a much lower rate 37.6%.17 But Ahmad Khan et al study showed moderately differentiated SCC as the most common variant.13 Regarding tumour dimension, in more than 34 cases the greatest diameter(53.12%) were 2-4 cm that is TNM stage T2.In Dragomir et al study too most of the tumors were of stage T2 (48.8%) but their incidence was slightly lower than seen in our study.17 Tumour site, size and invasive front pattern (non-cohesive front) and tumour thickness (greater than 5 mm) are reliable predictors for lymphnode metastases. O-charoenrat et al from his study had concluded that thickness > 5 mm was a reliable indicator of occult nodal metastases hence necessitates elective neck dissection.25 Regarding marginal clearance, 21 cases (32.81%) showed margin involvement in our study group. 50% of MDSCC showed margin involvement and it was the most common tumour showing margin involvement. Surgical clear margins > 5mm are recommended to prevent local recurrence.26 Histological grading along with the deep invasive border involvement pattern also influences the outcome of the disease. Tumours with pushing margins are lessaggressive when compared with tumours invading in a noncohesive front that is in tiny strands or single cells.27 Regarding lymph node metastasis, in our study 25 cases showed metastases. The mechanisms of spread are commonly by embolism, to a lesser extent by permeation and rarely skip metastasis. Extracapsular lymphnode spread also prove to be significant prognostic marker. Extranodal extension is a predictor of regional relapse and criteria for post-operative radiotherapy.28 According to Platz et al, tumour size and nodal deposits are the most significant prognostic factors.29 Laramore et al in his study had proved that two and more than two positive nodes, extracapsular extension in nodes and positive resection margins carries poor prognosis.30 11% of cases showed cortical bone invasion in their study which was slightly higher than our study. Vascular invasion also carries paramount prognostic importance.

 

CONCLUSION

Thus, from this study we come to a conclusion that squamous cell carcinoma well differentiated grade is the most common type in this area. This is due to increased awareness among the common people about oral cancer and early detection. Tumour size, nodal status, margin status and invasive front are the most important prognostic factors.

 

REFERENCES

  1. Mehrotra R, Pandya S, ChaudhariA,etal,Prevalence of oral premalignant and malignant lesions at a tertiary level hospital in Allahbad , India. Asian Pacific J Cancer Prev 2008;9:263-266.
  2. http://www.iarc.fr/en/media-centre/pr/2012/pdfs/pr210_E.pdf.Indian cancer statistics, a model to be followed. World health organization
  3.  Wong DTW, Todd R, Tsuji T, Donoff RB. Molecular biology of human oral cancer. Crit Rev Oral Biol Med. 1996; 7: 319–328
  4.  Sankaranarayanan R Oral cancer in India: An epidemiologic and clinical review Oral Surg Oral Med Oral Pathol 1990; 69(3):325-30
  5. Kuruvilla J Utilizing dental colleges for eradication of oral cancer in India Indian J Dent Res 2008; 19: 349-53
  6. Khan M, Khitab U. Histopathological gradation of oral squamous cell carcinoma in niswar(snuff) dippers. Pak Oral Dent. J 2005; 25: 173-6.
  7. Akram S, Mirza T, Mirza MA, Qureshi M. Emerging patterns in clinico-pathological spectrum of oral cancers. Pak J Med Sci 2013; 29: 783-7
  8. Iype EM, Pandey M, Mathew A, Thomas G, Sebastain P, Nair MK. Oral cancer among patients under the age of 35 years J Postgrad Med 2001;47:171-76
  9. Leon Barnes, John W. Eveson, Peter Reichart, David SidranskyWorld Health Organization Classification of Tumours Pathology and Genetics of Head and Neck Tumours IARC Press Lyon, 2005 163-175.
  10. Bundgaard T, Rossen K, Henriksen SD, Charabi S, Sogaard H, Grau C. Histopathologic parameters in the evaluation of T1 squamous cell carcinomas of the oral cavity. Head Neck 2002; 24(7):656–60. 10.
  11. Mehrotra R, Singh M, Kumar D, Pandey AN, Gupta RK, Sinha US. Age specific incidence rate and pathological spectrum of oral cancer in Allahabad. Indian J Med Sci. 2003; 57 (9): 400-4.
  12. Channanna C, SagarMugadur, and Ramesh K Socio-Demographic Factors and Oral Cancer: A Clinical Study RRJMHS 2014;3(4):159-16420.
  13. Ahmad Khan, Sartaj Khan, Umar KhitabEmerging Clinical And Histopathological Spectrum Of Oral Squamous Cell Carcinoma. JKCD 2015; 5(2):12-1515a. 
  14. Kiran G, Shyam NDVN, Rao J, Krishna A, Reddy B S, Prasad N. Demographics And Histopathological Patterns Of Oral Squamous Cell Carcinoma At A Teritiary Level Referral Hospital In Hyderabad, India.
  15. Khaleel M.E., Raza A., Ehsan A. Masood R. And Javed M. Clinicopathological Spectrum Of Oral Squamous Cell Carcinoma At A Public Sector Health Facility. Biomedica 2015; 31(1): 21-615.
  16. SaadiaAkramTalatMirzaM AamirMirza, and MasoodQureshi Emerging Patterns in Clinico-pathological spectrum of Oral CancersPak J Med Sci 2013; 29(3): 783–787.
  17. L. P. Dragomir, Cristiana Simionescu, Luminiţa Dăguci, Monica Şearpe, Manuela Dragomir. Clinical, Epidemiological And Histopathological Prognostic Factors In Oral Squamous CarcinomaCurrent health sciences journal 2016; 42(2): 201-5
  18. Smita S Masamatti, Alka V Gosavi Histopathological Study of Malignant Oral Tumours:A Five-Year Study. International Journal of Scientific Study 2016; 4(3): 30-34.
  19. Mirza T, Alam SM, Zaidi SH, Mirza T, Rafi T. Current status of Oral Cancer in Pakistan.Pak J Otolarnyngol. 1996;12:225–229.
  20. Brown LM, Check DP, Devesa SS. Oral cavity and pharynx cancer incidence trends by subsite in the United States: Changing Gender patterns. J Oncol. 2012;2012:649498. Epub.doi: 10.1155/2012/649498. 
  21. Deepa V. BabjiAlka D. KaleSeema R. Hallikerimath, and Vijayalakshmi S. KotrashettiHistomorphometric Study to Compare Histological Changes Between Oral Squamous Cell Carcinoma and Apparently Normal Adjacent Oral Mucosa. Indian J Otolaryngol Head Neck Surg. 2015 Mar; 67(Suppl 1): 21–28. 16.
  22. Su CC, Yang HF, Huang SJ. Distinctive features of oral cancer in Changhuacounty: high incidence, buccal mucosa preponderance, a close relation to betel quid chewing habit. J Formos Med Assoc 2007; 106: 225-33.
  23. Taghavi N, Yazdi I. Prognostic factors of survival rate in oral squamous cell carcinoma: Clinical, histologic, genetic and molecular concepts. Arch Iran Med. 2015; 18(5): 314 – 319
  24. Johan SI, Usha SI, Naveed QR. Histologic presentation of oral squamous cell carcinoma. Pak Oral Dent J 2004; 24: 95-6. 19.
  25. O-charoenrat P, Pillai G, Patel S, Ficher C, Archer D, EcclesS,et al. Tumor thickness predicts cervical nodal metastases and survival in early oral tongue cancer. Oral Oncol 2003;39:386-90.
  26. Liao CT, Chang JT, Wang HM, Ng SH, Hsueh C, Lee LY, et al. Analysis of risk factors of predictive local tumor control in oral cavity cancer. Ann Surg Oncol. 2008; 15(3): 915 – 922.
  27. Ravasz LA, Hordijk GJ, Slootweg PJ, Smit F, Van der Tweel I (1993). Uni- and multivariate analysis of eight indications for post-operative radiotherapy and their significance for local-regional cure in advanced head and neck cancer. J LaryngolOtol 107: 437-440.23.
  28. Kane SV, Gupta M, Kakade AC, D’cruz A. Depth of invasion is the most significant histological predictor of subclinical cervical lymphnodes metastasis in early squamous carcinomas of the oral cavity. Eur J Surg Oncol 2006;32:795-803.
  29. Platz H, Fries R, Hudec M (1985). Retrospective DOSAK Study on carcinomas of the oral cavity: results and consequences. J Maxillofac Surg 13: 147-153.
  30. Laramore GE, Scott CB, al Sarraf M, Haselow RE, Ervin TJ, Wheeler R, Jacobs JR, Schuller DE, Gahbauer RA, Schwade JG, Campbell BH (1992). Adjuvant chemotherapy for resectable squamous cell carcinomas of the head and neck: report on Intergroup Study 0034. Int J Radiat Oncol BiolPhys 23: 705-713.