Identification of the site for biopsy in oral mucosa cancer diagnostics

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INTRODUCTION

Annually, more than 355 thousand new cases of malignant neoplasms of the oral mucous membrane (OMM) are registered worldwide [1]. In 2018, OMM cancer, according to oncological morbidity, ranks 18th in the Russian Federation. In 2018, 9,518 patients were diagnosed with OMM cancer in Russia, including 199 patients in the Samara region. In all patients with malignant neoplasms of the OMM registered in the Russian Federation, the diagnosis was verified histologically in 97.9% of the cases [2].

Knowledge of the morphology and type of tumor growth is necessary when selecting treatment for patients with OMM cancer. From the standpoint of evidence-based medicine, cancer can be diagnosed only with biopsy sampling, followed by highly reliable histological examination [3]. Biopsy sampling should be performed according to strict indications, as it can lead to a number of adverse events. Diagnostic errors in OMM cancer, when obtaining a histological conclusion, can be made when taking study materials.

Biopsy of OMM formations is an invasive method of taking tissue specimens for histological examination for differential and definitive diagnoses [4]. This procedure is performed mainly in specialized health care institutions and is included in the standard and algorithm for examining patients with suspected oncopathology. The establishment of a correct diagnosis, subsequent timely treatment, and disease prognosis depend on the histological conclusion obtained [5].

Indications for biopsy of OMM formations should be justified and based on both subjective and objective data. Biopsy of OMM formations is performed by both incisional biopsy (IB), with removal of a part of the pathological tissue, and excision, with total removal of the pathological tissue and subsequent histological examination for verification and diagnosis. Excisional biopsy is performed when the tumor is small or the pathology is not yet verified after repeated IBs.

Difficulties in the morphological verification of a malignant process are largely associated with the biopsy technique, incorrect section of the macro preparation, and interpretation by a morphologist of an atypical tumor growth [6, 7, 8]. A recent study revealed that epithelial tumors of the OMM are most often diagnosed (98.5%) and represented by keratinizing squamous cell carcinoma [9].

The autofluorescent stomatoscopy (AFS) method has proven itself well for diagnostics of early forms of OMM cancer and demonstrated a high sensitivity in a number of studies. The use of autofluorescent methods for diagnosing cancer is currently promising because of its availability, non-invasiveness, and simplicity. According to scientific publications, in AFS rays, the precancer and cancer foci have a distinctive glow in the form of a dark spot [10, 11, 12, 13]. Since 2017, at the Samara Regional Clinical Oncology Center, to verify the diagnosis of cancer, materials for histological examination were examined using an autofluorescent lamp (AFS-400, Polironik, Moscow), glasses with a green light filter, and otorhinolaryngological conchotomes.

AIM

This study aimed to optimize the technique of IB using AFS in the diagnosis of OMM cancer.

MATERIAL AND METHODS

In this study, 89 outpatient records of patients examined at the Samara Regional Clinical Oncology Center in the period from 2017 to 2019 were analyzed; the patients had established diagnosis of OMM cancer of various localizations after IBs.

The inclusion criteria were patients initially referred to an oncologist for biopsy; exophytic papillary, ulcerative, and mixed forms of tumors; and verified OMM cancer.

The patients were distributed into two groups depending on the technique of IB and the histological verification (HV) of OMM cancer.

Patient groups were distributed by localization and histological type of the structure of the malignant process (Tables 1, 2). Indicators such as the biopsy rate, type of tumor growth, and disease stage were assessed. IB of OMM formations was performed to the main group (n = 43) under AFS until cancer was established histologically. Patients of the control group (n = 46) underwent single, second, and third IB of the OMM formations under direct vision until cancer was established histologically.

 

Таблица 1. Распределение больных по группам и локализации опухоли

Table 1. The distribution of the patients by group and location of the tumor

Localization	Group
	Control n = 46		Main n = 43
	n	%	n	%
Tongue	29	63	27	62
Alveolar part of the upper jaw	1	2	-	-
Alveolar part of the lower jaw	3	7	3	7
Oral cavity floor	8	17	7	16
Hard palate	3	7	2	5
Soft palate	1	2	2	5
Cheek	1	2	2	5
Total	46	100	43	100

Критерий Пирсона 2,221; р=0,988 [Pearson's criterion 2,221; p=0.988]

 

Таблица 2. Распределение больных в группах по полученным гистологическим результатам злокачественного процесса

Table 2. Distribution of patients in groups by the resulting histological data of the malignant process

Biopsy results	Group
	Control n = 46		Main n = 43
	n	%	n	%
Keratinizing squamous cell carcinoma	36	78	33	77
Non-keratinizing squamous cell carcinoma	9	20	9	21
Adenocystic cancer	0	0	1	2
Adenocarcinoma	1	2	0
Total	46	100	43	100

Критерий Пирсона 2,221; р=0,988 [Pearson's criterion 2,221; p=0.988]

 

The patients were 27–87 years old. The male-to-female ratio was 3:1 in the main group and 3:1 in the control group (p = 0.737). In both groups, IB was performed under local application, infiltration, and/or conduction anesthesia.

In the control group, IB with tissue removal from the pathological focus for histological examination was performed using otorhinolaryngological conchotomes at random under direct vision from the surface and along the edge of the pathological formations (Figure 1). In the main group, AFS was performed using an AFS-400 device and glasses with a green light filter. When using the lamp, precancer and cancer signs were assessed on a light scale, where a dark glow (dark spot effect) indicated the precancer and cancer foci.

 

Рисунок 1. Инцизионная биопсия опухоли слизистой щеки под контролем глаза с использованием оториноларингологического конхотома.

Figure 1. Incisional biopsy of cheek mucosa tumor under eye-control using an otorhinolaryngologic conchotome.

 

In the main group, biopsy was performed using otorhinolaryngological conchotomes under AFS control, and tissue samples were obtained from sites of pathological glow (dark spot) (Figure 2).

 

Рисунок 2. Инцизионная биопсия опухоли слизистой ретромолярного пространства с использованием лампы «АФС-400», очков с зеленым светофильтром и оториноларингологических конхотомов.

Figure 2. Incision biopsy of retromolar mucosa tumor using "APS-400" lamp, glasses with green light filter and otorhinolaryngological conchotomes.

 

After single IB in the control group, the diagnosis of cancer was confirmed in 25 (54%) patients, and after second and third incisions, the diagnosis was confirmed in 17 (37%) and 4 (9%) patients, respectively. In the main group, the AFS-400 lamp was used to identify more suspicious areas of the malignant process; after a single IB, the cancer was verified in 36 (84%) patients, and after repeated IB, it was verified in 7 (16%) patients (Figure 3).

 

Рисунок 3. Кратность биопсий и верификация диагноза.

Figure 3. Number of biopsies and diagnosis.

 

After single IB, HV of the tumor was made mainly in cases with a mixed type of tumor growth, i.e., in 17 (40%) and 15 (33%) cases in the main and control groups, respectively (p = 0.497) (Figure 4).

 

Рисунок 4. Кратность биопсий и верификация диагноза при смешанном типе опухолевого роста.

Figure 4. Number of biopsies and diagnosis verification for mixed tumor growth.

 

HV of exophytic-papillary tumor growth, which was the most difficult to verify, was obtained in 16 (37%) patients in the main group during primary biopsy and in 8 (17%) patients in the control group (p = 0.036) (Figure 5). Exophytic and ulcerative forms were diagnosed after a single IB in 3 (7%) and 2 (4%) cases in the main group, respectively (p = 0.591) (Figure 6).

 

Рисунок 5. Кратность биопсий и верификация диагноза при экзофитно-папиллярной форме опухолевого роста.

Figure 5. Number of biopsies and diagnosis verification in exophyte-papillar form of tumor growth.

 

Рисунок 6. Кратность биопсий и верификация диагноза при экзофитно-язвенной форме опухолевого роcта.

Figure 6. Number of biopsies and diagnosis verification in the exophite-lumen form of tumor growth.

 

The number of biopsies was also assessed depending on the stage of disease prevalence. After a single IB, HV of stage I–II cancer was achieved in 16 (37%) patients in the main group and in 8 (17%) patients in the control group (p = 0.036) (Figures 7, 8). After a single biopsy, the HV in patients with stages III–IV was diagnosed in 20 (47%) patients in the main group and in 17 (37%) patients in the control group (p = 0.361) (Figures 9, 10).

 

Рисунок 7. Кратность биопсий и верификация диагноза при I стадии.

Figure 7. Number of biopsies and diagnosis verification in stage I.

 

Рисунок 8. Кратность биопсий и верификация диагноза при II стадии.

Figure 8. Number of biopsies and diagnosis verification in stage II.

 

Рисунок 9. Кратность биопсий и верификация диагноза при III стадии.

Figure 9. Number of biopsies and diagnosis verification in stage III.

 

Рисунок 10. Кратность биопсий и верификация диагноза при IV стадии.

Figure 10. Number of biopsies and diagnosis verification in stage IV.

 

DISCUSSION

Recent research has revealed that the mucous membrane of the tongue is most often affected by cancer, and the percentage of advanced stages of OMM cancer is quite high. In our cases, tongue lesion was noted in 29 (63%) patients in the control group and in 27 (62%) in the main group (p = 0.981), and advanced stages were registered in 29 (63%) and 24 (56%) cases (p = 0.488), respectively [5]. A high percentage of malignant neoplasms of the OMM was represented by epithelial keratinizing squamous cell carcinoma in 36 (78%) cases in the control group and in 33 (77%) cases (p = 0.864) in the main group, which does not contradict published data [2, 4, 10].

Applying an optimized technique enabled HV of OMM cancer with a mixed type of growth in both groups without marked differences, with the exception of exophytic-papillary forms, which were found in 16 (37%) and 8 (17%) patients in the main and control groups, respectively (p = 0.036). HV of malignant tumors with exophytic-papillary forms and an initial stage of OMM cancer in the control group was difficult because the true pathological focus was not identified and elements of inflammation are present, which was demonstrated by the results obtained in the main group [10]. Moreover, after a single IB, the rate of verified cancer in initial stages in the main group was significantly higher than that in the control group, at 16 (37%) and 8 (17%), respectively (p = 0.036). To verify the diagnosis of cancer in initial stages, a third biopsy was required [10].

CONCLUSIONS

The autofluorescent complex AFS-400 and glasses with a green light filter for IB of OMM formations enable identification of suspicious sites for tissue sampling for histological examination and to obtain HV at the first biopsy in 84% of cases, taking into account the presence of stage I–II cancer in 16 (37%) patients and exophytic-papillary forms in 16 (37%) patients. This differs significantly from similar indicators in the control group (p = 0.036) and reduces the number of repeated IB.

Conflict of interest. The authors declare no conflict of interest.

About the authors

Andrei E. Orlov

Samara State Medical University; Samara Regional Clinical Oncology Dispensary

Email: Gabriel_002@mail.ru
ORCID iD: 0000-0003-3957-9526

PhD, Associate Рrofessor of the Department of Quality management and standardization of IPE, Chief physician

Russian Federation, Samara

Aleksei G. Gabrielyan

Samara State Medical University; Samara Regional Clinical Oncology Dispensary

Author for correspondence.
Email: Gabriel_002@mail.ru
ORCID iD: 0000-0002-5321-6070

assistant of the Department of Dentistry, IPE, maxillofacial surgeon

Russian Federation, Samara

Oleg I. Kaganov

Samara State Medical University; Samara Regional Clinical Oncology Dispensary; Penza Institute for Advanced Medical Education, branch of the Russian Medical Academy of Continuous Professional Education

Email: Gabriel_002@mail.ru
ORCID iD: 0000-0003-1765-6965

PhD, Professor, Department of Oncology, Deputy Chief physician of Samara Regional Clinical Oncology Dispensary, Head of the Department of Oncology and urology of Penza Institute for Advanced Medical Education

Russian Federation, Samara; Samara; Penza

Mikhail A. Postnikov

Samara State Medical University

Email: Gabriel_002@mail.ru
ORCID iD: 0000-0002-2232-8870

PhD, Associate Рrofessor of the Department of Dentistry of IPE

Russian Federation, Samara

Dmitrii A. Trunin

Samara State Medical University

Email: Gabriel_002@mail.ru
ORCID iD: 0000-0002-7221-7976

PhD, Professor, Department of Dentistry of IPE, Director of the Dental Institute

Russian Federation, Samara

Yuliya L. Denisova

Belarusian State Medical University

Email: Gabriel_002@mail.ru
ORCID iD: 0000-0003-0917-7972

PhD, Professor, Head of the Department of Therapeutic Dentistry

Belarus, Minsk

References

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