Indian Journal of Pathology and Microbiology
Home About us Instructions Submission Subscribe Advertise Contact e-Alerts Ahead Of Print Login 
Users Online: 1370
Print this page  Email this page Bookmark this page Small font sizeDefault font sizeIncrease font size

ORIGINAL ARTICLE Table of Contents  
Ahead of print publication
Histological risk score and its role in predicting recurrence in early-stage oral squamous cell carcinomas


1 Department of Pathology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India
2 Department of Surgical Oncology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad, Telangana, India

Click here for correspondence address and email

Date of Submission26-May-2021
Date of Acceptance07-Jun-2021
Date of Web Publication07-Jun-2022
 

   Abstract 


Context: Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cancers and is the most common carcinoma affecting the oral cavity. Early stage T1/T2 OSCC have a heterogeneous prognosis and a significant number of patients develop loco regional recurrence (LRR) and have reduced disease free survival (DFS) with increased disease related mortality. Aims and Objectives: To assess the impact of the three parameters used in Brandwein-Gensler risk model along with lympho-vascular invasion (LVI), depth of invasion (DOI) and lymph node metastases in predicting LRR in early stage OSCC. Materials and Methods: This was a retrospective study on early stage T1/2 OSCC patients over a period of 2 years who received treatment by surgical resection and had follow-up data. LRR was assessed based on recurrence of OSCC at the initial site or in regional lymph nodes. Results: Out of 1135 OSCC cases during our study period a total of 207 cases befitted our inclusion criteria. Recurrence was noted in 113 (54.6%) cases. Univariate analysis identified LVI (P < 0.00001), DOI (P < 0.00001), nodal involvement (P < 0.00001), worst pattern of invasion (WPOI) (P < 0.00001), lymphocytic host response (LHR) (P = 0.004), perineural invasion (PNI) (P = 0.012) as strong statistically significant risk factors for LRR. Conclusion: Adequate assessment of simple parameters on routine H and E by incorporating Brandwein-Gensler histological risk scoring model at the initial presentation can help prognosticate and predict LRR and select patients for post-surgical adjuvant therapy.

Keywords: Histological risk score, oral, squamous cell carcinoma


How to cite this URL:
Fonseca D, Khemani R, Pasam MK, Tagore R, Rao B V, Kodandapani S, Rao C, N. Raju K V, Rao T S. Histological risk score and its role in predicting recurrence in early-stage oral squamous cell carcinomas. Indian J Pathol Microbiol [Epub ahead of print] [cited 2023 Jan 29]. Available from: https://www.ijpmonline.org/preprintarticle.asp?id=346856





   Introduction Top


Oral cancer is a heterogeneous subgroup of head and neck malignant neoplasms affecting the lips, anterior two-thirds of tongue, salivary glands, gingiva, floor of the mouth, oral mucosal surface and palate, with the tongue being the most common location.[1] Based on GLOBOCAN 2020 data, oral cavity cancer has an incidence rate of 4.1% and mortality rate of 1.9% worldwide with an estimated number of 3,77,713 new cases and 1,77,757 deaths in 2020.[2] According to National Cancer Registry Program (NCRP), India, 2020, cancers of oral cavity and pharynx have an incidence rate of 1,39,018 with a crude rate of 19.2 and cumulative risk of 1 in 41 developing cancer at 0-74 years of age.[3]

Oral squamous cell carcinoma (OSCC) comprises more than 90% of oral cancers and is the most common carcinoma affecting the oral cavity.[1] Varied demographic, clinical and histopathological factors influence the prognosis of OSCC. The latest guidelines for treatment of OSCC include surgical resection followed by adjuvant chemotherapy and/or radiation depending on the stage of presentation, margin positivity and other prognostic factors. The 8th edition of American Joint Committee on Cancer (AJCC) classification has recently incorporated depth of invasion (DOI) and lymph node extra nodal extension (ENE) into its staging criteria where every 5 mm increase till ≥10 mm in DOI increases the T category by 1and pathologic ENE (+) upgrades the nodal category by 1.[4]

Early stage T1/T2 OSCC is usually treated by primary resection and elective nodal dissection with margin positivity being the most important prognostic factor. However due to their heterogeneous prognosis a significant number of patients develop loco regional recurrence (LRR) and have reduced disease free survival (DFS) with increased disease related mortality.[5],[6]

Despite significant research on the molecular biology of OSCC no specific biomarkers have been identified that could explain the heterogeneity of these tumors. This potentiates the need for further studies that could accurately predict their outcome and help in better patient management.[4] The Brandwein-Gensler risk model was proposed in 2005 as a modification and extension to previous histological models. This histologic risk assessment scoring model encompasses three major entities WPOI, LHR and PNI in predicting risk of recurrence. A total score of 3 or more is considered as high risk, 1–2 as intermediate risk and 0 as low risk.[4],[7]

Our study aims to assess the impact of these three parameters used in Brandwein-Gensler risk model along with lympho-vascular invasion (LVI), depth of invasion (DOI) and lymph node metastases in predicting LRR in early stage OSCC.


   Materials and Methods Top


This was a retrospective study carried out on early stage T1/2 OSCC patients classified as per the 8th edition of AJCC over a period of 2 years from January 2016 to December 2017. Only primary OSCC patients who received treatment by surgical resection and had follow-up data till January 2020 were included in the study.

The demographic parameters including age and gender were noted from the medical records. Hematoxylin and eosin-stained slides were retrieved from archival and risk scoring was performed using Brandwein-Gensler risk model [Table 1].[4],[8] Histological parameters including grade, WPOI, DOI, LHR, PNI, LVI and pathological stage and lymph nodal metastases in recurrent cases were reviewed and recorded. The pathologist performing histopathological assessment was blinded to clinical data variables and patient outcomes. LRR was assessed based on recurrence of OSCC at the initial site or in regional lymph nodes.[4]
Table 1: Brandwein-Gensler risk model[4],[8]

Click here to view


Statistical analysis

Descriptive statistics were used to summarize patient histological features and disease classification at diagnosis. All relevant data was entered into the excel sheet of Microsoft Excel. SPSS software, version 21.0 was used. Univariate analyses of the risk factors for LRR were performed using log-rank tests. A P value of <0.05 was considered to be statistically significant.


   Results Top


During our study period we had 1135 OSCC cases which included small biopsies, surgical resection specimens and referral cases. Out of these 1135 cases a total of 207 cases befitted our inclusion criteria and were taken as our study population. Based on 8th edition of AJCC criteria, 75 (36.2%) and 132 (63.8%) cases were divided into T1 and T2 stages respectively. The median age of presentation was 51 years. The most common site of initial presentation was the buccal mucosa followed by the tongue, alveolus, lip, retromolar trigone, gingiva buccal sulcus and palate in decreasing order of occurrence. Recurrence was noted in 113 (54.6%) cases. Tongue was the most common site of recurrence.

There was a male predilection in both primary (71%) and recurrent (76.1%) OSCC. The most common histologic subtype in all primary and recurrent OSCC cases was well differentiated OSCC [Table 2] and [Figure 1].
Figure 1: Gross images and representative photomicrographs depicting various parameters of early stage OSCC. Gross images of total glossectomy specimen showing a grey white ulceroinfiltrative lesion (a and b) and maxillectomy specimen showing a superficial grey brown ulceroproliferative lesion (c) with photomicrographs showing WD (d, H and E ×400), MD (e, H and E ×400), and PD (f, H and E ×400) early stage OSCC; WPOI 1 with pushing borders (g, h and E ×100), WPOI 2 with finger like growth (h, H and E ×400), WPOI 3 with large separate islands showing more than 15 cells per island (i, H and E ×400), WPOI 4 with small tumor islands showing 15 cells or fewer per island (j, H and E ×400), WPOI 5 with tumor satellites >1 mm from main tumor (k, H and E ×40), LHR type 1 (l, H and E ×400) and type 2 (m, H and E ×100), PNI around small (n, H and E ×400) and large nerves (o, H and E ×100), LVI (p, H and E ×100), measurement of DOI (q, H and E ×40) and lymph nodal metastasis (r, H and E ×400). OSCC: Oral squamous cell carcinoma, WD: Well differentiated, MD: Moderately differentiated, PD: Poorly differentiated, WPOI: Worst pattern of invasion, LHR: Lymphocytic host response, PNI: Perineural invasion, LVI: Lympho-vascular invasion, DOI: Depth of invasion

Click here to view
Table 2: The various parameters assessed including univariate analysis (log-rank tests) of the risk factors for LRR

Click here to view


Univariate analysis identified LVI (P < 0.00001), DOI (P < 0.00001), nodal involvement (P < 0.00001), WPOI (P < 0.00001) and LHR (P = 0.004) as strong risk factors for LRR. PNI (P = 0.012) and Brandwein-Gensler risk model (P = 0.019) were also statistically significant risk factors of LRR [Table 2].


   Discussion Top


Patients diagnosed with early stage OSCC have a heterogeneous prognosis and varied DFS.[4],[9],[10] This potentiates the need for further studies to validate and test a myriad of factors that can help predict the recurrence rate in these tumors.

In our study on early stage OSCC, the median age of presentation was 51 years with a male predominance in both primary (71%) and recurrent (76.1%) cases. The study done by Hori et al.[9] and Li et al.[5] had similar findings of median age of presentation of 61 and 63 years with a male predilection of 69% and 56% respectively. T1 and T2 stage tumors in the present study constituted 36.2% and 63.8% cases respectively. T1 and T2 tumors in the studies done by Hori et al.,[9] Li et al.[5] and Almangush et al.[8] constituted 56% and 44%, 61% and 39%, 44.3% and 55% respectively.

Previous studies done on early stage OSCC were predominantly conducted on unknown pathological nodal status, or without nodal status correlation.[6] In the present study data on nodal metastases was analyzed and found to be a statistically significant predictor of LRR [Table 2].

Univariate analysis identified LVI (P < 0.00001), DOI (P < 0.00001), nodal involvement (P < 0.00001), WPOI (P < 0.00001), LHR (P = 0.004), PNI (P = 0.012) and Brandwein-Gensler risk model (P = 0.019) as strong statistically significant risk factors for LRR [Table 2]. Hori et al.[9] identified blood vessel invasion (P = 0.03), lymphatic invasion (P < 0.001), WPOI (P < 0.001), and tumor budding and depth (P < 0.001) as histopathological risk factors for lymph node recurrence, and lymphatic invasion (P = 0.001), WPOI (P < 0.001), and tumor budding and depth (P < 0.001) as predictive factors for DFS. Li et al.[5] identified WPOI (P = 0.0002), LHR (P = 0.0297) and Brandwein-Gensler risk model (P = 0.0012) as histological risk factors for LRR [Table 3].
Table 3: Comparison of the present study with other studies

Click here to view


The present study is the largest single center study in this part of the world evaluating Brandwein-Gensler risk model in OSCC staged as per 8th edition of AJCC with focus on early-stage cases and in addition comparing LVI, DOI and lymph node metastases on recurrence.


   Conclusion Top


Early stage OSCC is associated with a heterogeneous prognosis. DOI, WPOI, LVI, nodal metastases, LHR, PNI and Brandwein-Gensler risk model can be considered as strong independent risk factors for predicting LRR. Adequate assessment of simple parameters on routine H and E by incorporating Brandwein-Gensler histological risk scoring model at the initial presentation can help prognosticate and predict LRR and select patients for post-surgical adjuvant therapy.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
Migueláñez-Medrán BC, Pozo-Kreilinger JJ, Cebrián-Carretero JL, Martínez-García MA, López-Sánchez AF. Oral squamous cell carcinoma of tongue: Histological risk assessment. A pilot study. Med Oral Patol Oral Cir Bucal 2019;24:e603-9.  Back to cited text no. 1
    
2.
Globocan S. Lip, oral cavity. Iarc.fr. Available from: https://gco.iarc.fr/today/data/factsheets/cancers/1-Lip-oral-cavity-fact-sheet.pdf. [Last accessed on 2021 May 9].  Back to cited text no. 2
    
3.
Mathur P, Sathishkumar K, Chaturvedi M, Das P, Sudarshan KL, Santhappan S, et al. Cancer statistics, 2020: Report from National Cancer Registry Programme, India. JCO Glob Oncol 2020;6:1063-75.  Back to cited text no. 3
    
4.
Thakur R, Thakar A, Malhotra RK, Sharma A, Kakkar A. Tumour-host interface in oral squamous cell carcinoma: Impact on nodal metastasis and prognosis. Eur Arch Oto Rhino Laryngol 2021. doi.org/10.1007/s00405-021-06756-y.  Back to cited text no. 4
    
5.
Li Y, Bai S, Carroll W, Dayan D, Dort JC, Heller K, Jour G, et al. Validation of the risk model: High-risk classification and tumour pattern of invasion predict outcome for patients with low-stage oral cavity squamous cell carcinoma. Head Neck Pathol 2013;7:211-23.  Back to cited text no. 5
    
6.
Parekh D, Kukreja P, Mallick I, Roy P. Worst pattern of invasion–type 4 (WPOI-4) and Lymphocyte host response should be mandatory reporting criteria for oral cavity squamous cell carcinoma: A re-look at the American Joint Committee of Cancer (AJCC) minimum dataset. Indian J Pathol Microbiol 2020;63:527-33.  Back to cited text no. 6
[PUBMED]  [Full text]  
7.
Brandwein-Gensler M, Teixeira MS, Lewis CM, Lee B, Rolnitzky L, Hille JJ, et al. Oral squamous cell carcinoma: Histologic risk assessment, but not margin status, is strongly predictive of local disease-free and overall survival. Am J Surg Pathol 2005;29:167-78.  Back to cited text no. 7
    
8.
Almangush A, Bello IO, Coletta RD, Mäkitie AA, Mäkinen LK, Kauppila JH, et al. For early-stage oral tongue cancer, depth of invasion and worst pattern of invasion are the strongest pathological predictors for locoregional recurrence and mortality. Virchows Archiv 2015;467:39-46.  Back to cited text no. 8
    
9.
Hori Y, Kubota A, Yokose T, Furukawa M, Matsushita T, Oridate N. Association between pathological invasion patterns and late lymph node metastases in patients with surgically treated clinical N0 early oral tongue carcinoma. Head Neck 2020;42:238-43.  Back to cited text no. 9
    
10.
Chatterjee D, Bansal V, Malik V, Bhagat R, Punia RS, Handa U, et al. Tumour budding and worse pattern of invasion can predict nodal metastasis in oral cancers and associated with poor survival in early-stage tumors. Ear Nose Throat 2019;98:E112-9.  Back to cited text no. 10
    

Top
Correspondence Address:
Daphne Fonseca,
Consultant Pathologist, Department of Pathology, Basavatarakam Indo American Cancer Hospital and Research Institute, Hyderabad - 500 034, Telangana
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ijpm.ijpm_514_21



    Figures

  [Figure 1]
 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

Top
 
  Search
 
  
  
 Article in PDF
     Search Pubmed for
 
    -  Fonseca D
    -  Khemani R
    -  Pasam MK
    -  Tagore R
    -  Rao B V
    -  Kodandapani S
    -  Rao C
    -  N. Raju K V
    -  Rao T S


    Abstract
   Introduction
    Materials and Me...
   Results
   Discussion
   Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed607    
    PDF Downloaded26    

Recommend this journal