|Year : 2020 | Volume
| Issue : 3 | Page : 215-217
The stromal dictators in a concomitant case of oral submucous fibrosis - Oral Squamous Cell Carcinoma
Anupama Mukherjee, Anita Spadigam, Anita Dhupar
Department of Oral and Maxillofacial Pathology, Goa Dental College and Hospital, Bambolim, Goa, India
|Date of Submission||24-Jun-2019|
|Date of Decision||24-Mar-2020|
|Date of Acceptance||06-Jun-2020|
|Date of Web Publication||11-Jul-2020|
F-1 Oasis, Nagali Hills Colony, Dona Paula, Panaji - 403 004, Goa
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Oral submucous fibrosis (OSMF) is a potentially malignant disorder, characterized by alteration in the connective tissue stroma. Its association with oral squamous cell carcinoma (OSCC) has been recognized and conferred a special status as a distinct disease entity with improved prognosis as compared to conventional squamous cell carcinoma. Such cases of concomitant presentation of OSMF and OSCC have not yet been defined, leading to ambiguity regarding the evaluation. The concomitant occurrence of OSMF-OSCC is associated with histopathological features, unlike OSMF, yet similar to an aggressive presentation of OSCC. An indepth evaluation of the connective tissue, along with other tumor characteristics such as tissue hypoxia, inflammatory cell population, neoangiogenesis, and stromal cells fortify the possibility of these cases of concomitance being as aggressive, if not more, as compared to conventional OSCC. Thus, recognizing such cases along with the evaluation of probable prognostic indicators is necessary to improve the current understanding of tumorigenesis and progression in concomitant cases of OSMF-OSCC.
Keywords: Aggressiveness, concomitant oral submucous fibrosis and oral squamous cell carcinoma, tumor microenvironment
|How to cite this article:|
Mukherjee A, Spadigam A, Dhupar A. The stromal dictators in a concomitant case of oral submucous fibrosis - Oral Squamous Cell Carcinoma. Int J App Basic Med Res 2020;10:215-7
|How to cite this URL:|
Mukherjee A, Spadigam A, Dhupar A. The stromal dictators in a concomitant case of oral submucous fibrosis - Oral Squamous Cell Carcinoma. Int J App Basic Med Res [serial online] 2020 [cited 2020 Aug 4];10:215-7. Available from: http://www.ijabmr.org/text.asp?2020/10/3/215/289469
| Introduction|| |
India continues to bear about one-third of the global burden of oral cancer, with an incidence of nearly 1 lakh cases each year. Oral squamous cell carcinoma (OSCC) is often preceded by oral potentially malignant disorders (OPMDs).
Oral submucous fibrosis (OSMF) is one such OPMD which is highly prevalent in South-east Asia and is characterized by the changes in collagen fibers. Paymaster first reported the possible precancerous nature of OSMF. Variable figures derived from studies on the Indian population have reported the malignant transformation rate of OSMF between 4.5%–7.6%,, and more recently as 0.2%–1.2% with a globally accepted rate of 7%–13%.
The authors have reported the cases of OSCC along with OSMF as early as 1968. An entity such as concomitant OSMF-OSCC has also been reported with a prevalence of 25.77%. Due to the lack of a clear definition of “concomitance” in this scenario, we propose to define it as cases that present, at a point in time, with the clinical features of OSMF along with a lesion that is histopathologically proven as OSCC. These cases of concomitant OSMF-OSCC have been reported in younger males demonstrating a better grade of OSCC differentiation with lesser nodal metastasis. Ray et al. and Chaturvedi et al. have regarded such cases as a distinct clinicopathological entity owing to its proposed areca-associated pathogenesis, hypothesized extracellular matrix alterations,, and an overall better prognosis.
| Case Report|| |
A 47-year-old male presented with a swelling on the right side of the face along with a history of burning sensation for 1 month. The patient was a betel quid and tobacco habitué for the past 25 years.
On examination, the labial and buccal mucosa showed pallor, blanching along with bilateral and circumoral bands. The right buccal mucosa showed the presence of an ulceroproliferative lesion, measuring 3 cm × 2 cm. It had an indurated base was tender and bled on touch. Examination of regional lymph nodes revealed a single submental node and matted right submandibular nodes, both measuring 1.5 cm. They were fixed and tender. Contrast computed tomography of the neck revealed enlargement of level IB, level II, and prehyoid nodes.
Incisional biopsy reported a moderately differentiated squamous cell carcinoma. The stroma demonstrated minimal fibrosis, absence of hyalinization along with numerous budding capillaries, and moderate-to-dense chronic inflammatory cell infiltrate [Figure 1]. Perineural and perivascular invasion was noted. The above histopathological findings of OSCC when viewed in the context of clinically existent OSMF raise a query regarding the epithelial and stromal alterations that probably impact the prognosis and management. Thus, an analysis of the associated stromal alterations was undertaken to better understand the unique tumor microenvironment in cases of concomitance.
|Figure 1: (a) Section of invasive front (H and E, x100) (b) Masson's trichrome|
Click here to view
Using Masson's trichrome (histochemistry) for the assessment of early and mature collagen, minimal fibrosis, and absence of areas of hyalinization was confirmed [Figure 1]. Immunohistochemistry for the key microenvironmental features such as the presence of myofibroblasts, protumoral macrophages, extent of neoangiogenesis, and tissue hypoxia was investigated [Figure 2]. The stroma showed minimal positivity for α-smooth muscle actin (α-SMA) with most areas being obscured by dense inflammation. A 2 + distribution of CD-163(+) cells was noted, particularly around tumor islands, demonstrating diffuse infiltration of M-2 protumoral macrophages. CD-105, a marker specific for neoangiogenesis, highlighted the presence of numerous budding capillaries at the invasive front in the intervening stroma. Diffuse positivity for hypoxia-inducible factor (HIF-α) was noted throughout the epithelium and tumor islands. The evaluated stromal features are suggestive of an aggressive phenotype, creating a dilemma for prognostication.
|Figure 2: (a) Minimal positivity for smooth muscle actin (×400) (b) Positivity for CD-163 (TAM's) (×400) (c) HIF-α positive epithelium and tumor islands (×100) (d) CD-105 positive blood vessels (×400)|
Click here to view
| Discussion|| |
OSMF predominantly and progressively involves the connective tissue compartment of the oral mucosa. Cases showing the progressive development of an epithelial pathology such as OSCC justify the categorization of OSMF as an OPMD.
The present case is in concurrence with the data reported by Bhola et al. who compared concomitant cases of OSMF-OSCC with the cases of OSCC only and examined the possibility of a better prognosis of the former. Much has been stated regarding the prognostic factors for OSCC, whereas prognostic indicators for OSCC concomitant with OSMF are yet to be explored. Limited data are available regarding the stromal modifications and behavior of concomitant cases.
We focused on four primary and relevant aspects of the tumor stroma in the scenario of concomitance. It has been hypothesized that fibrosis, as noted in OSMF, leads to claudication of blood vessels, resulting in a decrease in perfusion to the tissues. This has been regarded as a rate limiting step for tumorigenesis and spread, thus improved prognosis. While the exact mechanism has not been elicited, a similar effect of fibrosis on the lymphatic system lowers the incidence of nodal involvement.
Siriwardena et al. have reported no association between the degree of fibrosis and malignant transformation or the former and tumor differentiation. Alka et al. noted no significant variation in the expression of SMA between the cases of concomitance and OSCC alone. The minimal amount of fibrosis and the absence of hyalinization as in the current case is an intriguing finding when viewed in the context of OSMF and OSCC. The same is corroborated by the minimal positivity for SMA and demands inquiry into the underlying stromal process that leads to such contrasting findings.
The diffuse positivity for HIF-α in this case is in agreement with the increase in hypoxia as reported by Chaudhary et al. CD-105-positive vessels are suggestive of a metabolic shift and an attempt of the stroma to cope with the increase in demand for tissue perfusion. No previous data regarding the inflammatory component in such cases of OSMF-OSCC exist a protumoral infiltrate of M2 macrophages was noted. The aggressive nature of the lesion in this particular case is fortified by the extensive involvement of lymph nodes and the rapid progression of the disease.
While it may be premature to attribute a better prognosis to concomitant cases, further investigation regarding the clinical course of the disease along with the tumor microenvironment is warranted [Figure 3]. As illustrated through this case, in the concurrent scenario of OSMF-OSCC, alterations in the tumor stroma may actually potentiate the aggressiveness of the tumor and alter expected behavior.
|Figure 3: A diagnostic work up for concomitant cases of oral submucous fibrosis oral squamous cell carcinoma must include clinical staging and histopathological evaluation of the epithelial and stromal alterations that drive tumorigenesis and progression|
Click here to view
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chourasia NR, Borle RM, Vastani A. Concomitant association of oral submucous fibrosis and oral squamous cell carcinoma and incidence of malignant transformation of oral submucous fibrosis in a population of central India: A retrospective study. J Maxillofac Oral Surg 2015;14:902-6.
Sarode SC, Chaudhary M, Gadbail A, Tekade S, Patil S, Sarode GS. Dysplastic features relevant to malignant transformation in atrophic epithelium of oral submucous fibrosis: A preliminary study. J Oral Pathol Med 2018;47:410-6.
Pundir S, Saxena S, Aggrawal P. Oral submucous fibrosis a disease with malignant potential – Report of two cases. J Clin Exp Dent 2010;2:2-5.
Pindborg JJ, Mehta FS, Gupta PC, Daftary DK. Prevalence of oral submucous fibrosis among 50,915 Indian Villagers. Br J Cancer 1968;22:646-54. doi: 10.1038/bjc.1968.76.
Ray JG, Ranganathan K, Chattopadhyay A. Malignant transformation of oral submucous fibrosis: Overview of histopathological aspects. Oral Surg Oral Med Oral Pathol Oral Radiol 2016;122:200-9.
Tilakaratne WM, Klinikowski MF, Saku T, Peters TJ, Warnakulasuriya S. Oral submucous fibrosis: Review on aetiology and pathogenesis. Oral Oncol 2006;42:561-8.
Chaturvedi P, Malik A, Nair D, Nair S, Mishra A, Garg A, et al
. Oral squamous cell carcinoma associated with oral submucous fibrosis have better oncologic outcome than those without. Oral Surg Oral Med Oral Pathol Oral Radiol 2017;124:225-30.
Ekanayaka RP, Tilakaratne WM. Oral submucous fibrosis: Review on mechanisms of pathogenesis and malignant transformation. J Carcinogene Mutagene 2013;S5:1-11. Avaliable from: http://dx.doi.org/4172/2157-2518.S5-002
. [Last assessed on 2015 Aug 22].
Alka HH, Prajakta ZR, Minal CS, Madhuri GN, Patil Swati AA. Immunohistochemical analysis of tumor-associated stroma in oral squamous cell carcinoma with and without preexisting oral submucous fibrosis. J Datta Meghe Inst Med Sci Univ 2018;13:91-4.
Bhola N, Bhutekar U, Jadhav A. Is OSMF is an independent variable to affect cervical metastasis in OSCC associated with OSMF. Sch J Dent Sci 2017;4:140-3.
Siriwardena BSMS, Jayawardena KLTD, Senarath NH, Tilakaratne WM. An Evaluation of Clinical and Histopathological Aspects of Patients with Oral Submucous Fibrosis in the Background of Oral Squamous Cell Carcinoma. Hindawi, BioMed Research International 2018. Article ID 4154165. 7 pages. https://doi.org/10.1155/2018/4154165
Chaudhary M, Bajaj S, Bohra S, Swastika N, Hande A. The domino effect: Role of hypoxia in malignant transformation of oral submucous fibrosis. J Oral Maxillofac Pathol 2015;19:122-7.
] [Full text]
[Figure 1], [Figure 2], [Figure 3]