Differential diagnosis of papillary tumor of the tongue in a 71-year-old man finally diagnosed as verrucous squamous cell carcinoma of the tongue

Introduction

Verrucous cell carcinoma (VC) is a rare, well-diversified variant of squamous cell carcinoma (SCC). It is characterized by slow growth and rarely gives distant metastases. It may develop on erythroplakia, leukoplakia and proliferative verrucous leukoplakia (PVL). The risk factors for tongue cancer are smoking, alcohol abuse, tobacco chewing and poor oral hygiene [1]. The contribution of human papillomavirus (HPV virus) to the development of this type of cancer is controversial. Many authors have suggested a relationship between HPV 6, 11, 16 and 18 infection and VC [2], while in the paper [3] it has been demonstrated that VC does not meet the criteria justifying such a correlation. However, there is a correlation between the occurrence of SCC and HPV infection (type 16, 18). The differential diagnosis should take into account both benign and malignant tumors, which will be discussed further in this paper.

Case report

A 71-year-old patient noticed a lesion on the right side of the body of the tongue about 10 years ago. At that time it was a tumor with a diameter of about 1 cm, with pain in the tongue. For this reason, he went to the local otolaryngologist, and the doctor recommended a check-up visit, which the patient has missed. In 2014, the patient was admitted to the regional hospital, where the specimens from the lesion were taken. Fragments of stimulated, thickened stratified squamous epithelium with hyper- and parakeratosis and subepithelial chronic inflammatory infiltration were found. In 2018, the patient observed an enlargement of the tumor and reduced tongue mobility. In October 2018, the patient was admitted again to the ENT department, where under local anesthesia, samples were taken from the tumor of the tongue on the right side. It was identified as “fragments of inflammatory stroma, covered with thickened stratified squamous epithelium with parakeratosis, with no clear atypes and no visible divisional figures, p53 (–). The whole picture supports the benign character of the lesion – a fragment of the papilloma. A magnetic resonance imaging (MR) of the craniofacial face was also performed, and the image was described as “Within the body of the tongue, a heterogeneous area located on the right side of the body of the tongue, with a differentiated signal and dimensions of 33 mm × 27 mm × 29 mm. This area shows a heterogeneous signal. It exposes the edge of the tongue to the right, which is uneven. It is subject to heterogeneous strengthening, mainly peripheral. Conclusions: tumor of the tongue on the right side. Squamous cell carcinoma should be considered first”. In November 2018, due to the suspicion of malignant lesion in the patient, samples were collected again under local anesthesia. Diagnosis was as follows: “covered with acanthotic expanded stratified squamous epithelium with hyperkeratosis, partially papillary in appearance. Focal epithelial cells show features of dysplasia. The whole picture speaks in favor of the PVL – proliferative verrucous leukoplakia. Formerly known as florid papillomatosis”. In January 2019, the patient was admitted to the Department of Otolaryngology, Head and Neck Surgery in Poznań for further diagnostics. The ENT examination revealed an exophytic tumor with an uneven surface covering the right side of the tongue, infiltrating the left side, palpating the hard tongue with significantly reduced mobility, a tender infiltration of the oral cavity reaching the tongue base on the right side (fig. 1). The patient has a history of hypertension and nicotinism – about 10 cigarettes per day for 55 years. The patient reported a rapid increase of the lesion and a gradual reduction of tongue mobility since 2018. At the time of admission, he also reported dysphagia and odynophagia. The following tests were ordered: hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV) (negative) and Epstein Barr virus (EBV) (IgM negative, IgG positive) and the procedure was performed. During surgery under general anesthesia, numerous deep fragments of the tumor were collected from the right side of the tongue (fig. 2). The material was sent for intraoperative examination, but no cancer lesions were found, but in the postoperative examination it was diagnosed: verrucous squamous cell carcinoma. The reaction with p16 was also performed – a positive result was obtained, indicating HPV infection. Enhanced diagnostics was implemented in order to assess the stage of the cancer process. Computer tomography of the face, neck and chest was performed, where “weakly strengthening, polycyclic tumor of the whole body of the tongue, partially covering the base of the tongue” was described (fig. 3). The description further read: “without the infiltration of the diaphragm of the oral cavity, the lingual and tonsil angles and the mandible. Metastatic lymph nodes on the left side in IIA and III region”. There were no metastases in the chest or abdominal cavity. By the decision of the medical council, the patient was referred for radiotherapy.

Discussion

Diagnostics of tongue tumors should be based on a thorough laryngological examination, including palpation. Mucous membrane, ulceration, cohesiveness of the lesion, its displacement in relation to the floor, infiltration of surrounding structures, tongue mobility should be evaluated. The golden standard in differential diagnosis is histopathological examination. Computed tomography or magnetic resonance imaging (MR) should be performed. Pantomography should be considered to assess mandibular infiltration, or ultrasound of the neck with a possible fine needle aspiration biopsy (BAC) to assess the presence of lymph node metastases. Positron emission tomography (PET) does not play a role in the initial diagnosis. Patients with advanced lesions should be referred to chest CT to exclude metastatic lesions [4]. The presence of HBV, HCV, HIV, EBV or HPV infections can also be determined.
Differential diagnosis should include papillomas, papillomatosis (multiple papillomas), condyloma acuminatum, focal epithelial hypertrophy, keratoacanthoma, PVL, exophytic squamous cell carcinoma and verrucous squamous cell carcinoma [5]. Selected aspects are discussed below.
The occurrence of papillomas, papillomatosis, condyloma acuminatum and focal epithelial hypertrophy is associated with the HPV infection, most often type 32 and 33. This virus (especially type 16 and 18) may also contribute to precancerous lesions (leukoplakia) and cancer (squamous cell carcinoma). Papillomas are usually exophytic tumors, but they may also be flat keratinized and nonkeratinized lesions [6].
Leukoplakia is noticeable, clinically characterized, white spots, indelible from the mucosa, which are not clinically and macroscopically diagnosed as other disease entities [7]. It is a defensive reaction of the organism to irritants, such as smoking, alcohol, syphilis, vitamin deficiency, galvanic stream, chronic friction, ultraviolet radiation and oral candidiasis. Leukoplakia is a mild change in 80% of cases. The remaining cases are dysplastic changes – pre-cancer and cancer. Leukoplakia at the floor of the oral cavity, ventral and lateral surface of the tongue, palate and lips is most susceptible to malignant transformations. The World Health Organization (WHO) divides leukoplakia into two large groups: homogeneous and non-homogeneous. Non-homogeneous leukoplakia is divided into erythroplakia, nodular, spotted and papillary [8]. Proliferative verrucous leukoplakia is one of the variants of leukoplakia. It is characterized by papillary hypertrophy and high risk of neoplastic transformation.
Approximately 70% of these lesions turn into cancer. It is more common in women over 60 years of age. Smoking does not increase the risk of its appearance. A link between this leukoplakia and HPV infection has been observed. It has an image of white and papillary extensive lesion similar to hypertrophy in common papillae. It is characterized by slow growth and frequent recurrence after surgical removal [7, 8].
Oral hairy leukoplakia most often occurs on the lateral surface of the tongue in the form of white elevated lesions. Epstein-Barr virus multiplying in epithelial cells is responsible for this disorder. It is characteristic for people with HIV and people with immunosuppression. It is usually asymptomatic. It is a mild and self-limiting condition. In physical examination it may have a characteristic image resembling a washboard – alternately changed white folds and dimples of a normal pink mucous membrane. These stripes may merge. The treatment is based on antiviral drugs and immunosuppressive therapies [7, 8].
Verrucous carcinoma (VC) is a rare, highly differentiated type of squamous cell carcinoma. It is most commonly found in the oral cavity, cheek and lower gum mucosa. It was also observed in the nasal, laryngeal and esophageal cavities. The etiology and pathogenesis of this neoplasm is not fully explained, however, the literature indicates a correlation between the occurrence of VC and long-term smoking and chewing of tobacco, poor oral hygiene as well as excessive alcohol consumption. VC is characterized by slow, local growth, rarely metastasizes distantly, but may infiltrate surrounding structures such as bones and cartilages [9]. In physical examination it is described as a cauliflower tumor or a nodular lesion. The treatment of choice is a broad margin excision of the tumor. Long-term prognosis is better than in squamous cell carcinoma [8].
The occurrence of verrucous carcinoma simultaneously with squamous cell carcinoma (so-called hybrid verrucous squamous cell carcinoma) was demonstrated in about 20% of VC cases. Such a diagnosis was also made in this case. This could explain the metastases in the neck lymph nodes and the HPV infection in the tumor cells, which is not characteristic for VC. There are no clear guidelines for the treatment of hybrid tumors [2]. Many specialists should be involved in establishing the treatment plan – the ENT specialist, oncologist, pathomorphologist, radiotherapist and chemotherapist. The resectability of the tumor (the possibility of obtaining a sufficient margin of healthy tissue, safe margin is 5 mm, narrow margin is 1–3 mm, and positive margin < 1 mm) as well as individual conditions of the patient should be taken into consideration. In the absence of contraindications, surgical resection of the tumor with possible reconstruction is the treatment of choice. In case of suspected lymph node metastases, lymphadenectomy should be performed. In case of extensive lesions with subsidiary treatment (radiotherapy, chemotherapy) [4]. Radiotherapy is recommended in case of extensive tumor infiltration or in case of contraindications for surgical treatment.

Conclusions

In the discussed case, due to the long, 10-year time after the occurrence of the first symptoms, neoplastic transformation of initially benign papillary lesions could have occurred. It is also possible that the tissue samples were taken too superficially. An important role in establishing the correct diagnosis is played by properly collected material for histopathological examinations, its thorough evaluation by an experienced pathologist and additional examinations, including imaging. In case of symptoms that may indicate malignant character of the lesion (extensive infiltration, restricted mobility of the tongue, dysphagia, odynophagia), the correct diagnosis should be achieved and the treatment should be implemented as soon as possible. The most important task in differential diagnosis is to determine whether the observed change is malignant.

Funding

No external funding.

Ethical approval

Not applicable.

Conflict of interest

The authors declare no conflict of interest.

References