Abstract
Oral papillary squamous cell carcinoma (PSCC) is an unusual variant of squamous cell carcinoma with a better prognosis. The most common location of PSCC in the oral cavity is the gingiva and buccal mucosa, and it is exceedingly rare in the tongue. Herein, we present a case of PSCC in an 85-year-old male with a history of heart transplant and long-term use of immunosuppression medication. A verrucous pedunculated mass measuring 3.5 cm in the greatest dimension was present on the tip of tongue and a partial glossectomy was performed. Histological diagnosis was well differentiated PSCC with focal and minimal stalk invasion. No vascular nor perineural invasion was identified. Based on the current WHO and AJCC oral cancer staging system, the tumor stage was T2N0M0. The tumor cells were focally positive for p16, but in situ hybridization was negative for low-risk HPV (types 6 and 11) and high-risk HPV (types 16, 18, 31, 33 and 51). To the best of our knowledge, this is the first documented case of PSCC present on the tip of tongue in patients with long-term immune suppression. The pathogenesis, stage and prognosis of this entity are discussed. More case studies with long-term follow up are needed to achieve an accurate tumor stage and definite prognosis.
- Tip of tongue
- papillary squamous cell carcinoma
- heart transplant
- p16 immunohistochemistry
- HPV in situ hybridization
Papillary squamous cell carcinoma (PSCC) is an infrequent subtype of squamous cell carcinoma (SSC) (1, 2). Only a few cases of intraoral PSCC have been reported in the English literature. Clinically, PSCC can mimic verrucous carcinoma (VC) in its papillary and verrucoid appearance; however, VC does not have significant atypical cytologic changes of PSCC (3-5). In this paper we present a case of an unusual PSCC on the tip of the tongue in an 85-year-old male who had a history of heart transplant and was on immunosuppression medication for 20 years. The patient underwent partial glossectomy and was diagnosed as a pedunculated PSCC with minimal stalk invasion with a tumor stage of T2N0M0. Due to the rarity of such variant of SCC in this specific location, the diagnosis, pathogenesis, stage and prognosis of PSCC are discussed.
Case Presentation
An 85-year-old male was referred to ENT department for evaluation due to a growing mass on the tip of the tongue for approximately 10 weeks. The patient reported a burning sensation in the location of the mass. He denied any associated symptoms of dysphagia, dysphonia, sore throat or neck swelling. The patient was a cigar smoker (1-2 cigars daily) for 40 years and would drink a glass of wine every day. His main past medical history included arthritis, blood transfusion, cholelithiasis, cataract, hypertension, heart attack, congestive heart failure, stage 3 renal failure, and multiple melanomas. He underwent heart transplant twenty years ago and was on antihypertensive and anticoagulant medication as well as cyclosporine for immunosuppression.
Computed tomography (CT) scans showing a mass (arrows) with focal enhanced rim at the tip of the tongue (A, sagittal; B, axial).
Physical examination revealed an exophytic pedunculated verrucous mass measured 3.5 cm in the greatest dimension on the tip of the tongue. Head and neck computed tomography (CT) scans showed a hypoattenuating mass with a focal slightly enhancing rim at the tip of tongue (Figure 1A and 1B) and PET/CT were within normal limits without any additional mass or lymphadenopathy. After discussion in ENT-Head and Neck tumor board, a partial glossectomy with complex closure was performed and the specimen submitted for pathologic evaluation.
Pathology. Grossly, a 3.5×3.0×1.1 cm pedunculated, crusted and verrucoid mushroom-like mass covered by a glistening, villiform, pink-red mucosa on the dorsal aspect and a smooth, pink-red mucosa on the ventral aspect. The margins were inked and the cut surfaces of the mucosal lesion were nodular, tan-white and keratotic, and the tumor had a 1.0×1.0×0.1 cm thick stalk that was at least 1.2 cm from all peripheral resection margins. The tumor appeared superficially invasive into the underlying connective tissue at the stalk. The specimen was entirely submitted for histologic assessment. Microscopic examination at low-power magnification revealed an exophytic mass focally invading the underlying connective tissue core (Figure 2A). The invasive islands extended to the stalk of the exophytic mass with close proximity to the regional skeletal muscles of the tongue. High power magnification showed cytological atypical changes, including abundant eosinophilic cytoplasm, increased nuclear/cytoplasmic ratio, nuclear pleomorphism, hyperchromatism, vesicular nuclei and prominent nucleoli (Figure 2B and C). No evidences of lymphovascular invasion or perineural invasion were identified. Immunohistochemical stain for p16 showed positivity in 60% of the tumor cells (Figure 2D). In situ hybridization (ISH) for HPV was performed and was negative for low-risk (types 6 and 11) and high-risk (types 16, 18, 31, 33 and 51) HPV. Based on College of American Pathologists (CAP) protocol and AJCC 8th Edition, the final pathological diagnosis was PSCC with stage pT2N0M0.
Post-surgery the patient recovered very well. In the three months follow up, the patient was doing well and no recurrent tumor identified. PT/CT scan did not show any enlarged lymph nodes or metastatic masses.
Discussion
Papillary squamous cell carcinoma (PSCC) of the head and neck is a distinctive form of conventional squamous cell carcinoma that has a favorable prognosis in spite of its high recurrence rate (6). To the best of our knowledge, this is the first reported PSCC case involving tip of the tongue in English literature.
Histology and immunoreactivity of the PSCC. A-C: H&E stain showing pedunculated (A) well differentiated squamous cell carcinoma with keratin pearls invading the stalk connective tissue (A-C), (A, 1×; B and C, 200×); D: P16 immunoreactivity positive in 60% of tumor cells (200×).
Cases of PSCC of the oral cavity have been rarely reported. Yang et al. found that most of the PSCC develop in the gingiva and buccal mucosa (7). Those lesions demonstrate exophytic nature of growth and less invasiveness, the factors that make their prognosis better in comparison to conventional SCC (7). In the present case, the verrucous tumor showed significant cytologic atypia and desmoplasia but the neoplastic islands barely invaded to the proximity of submucosal connective tissue with no skeletal muscle invasion identified. There was no evidence of perineural or lymphovascular invasion.
The mechanism of pathogenesis of oral PSCC still remains to be elucidated. The host immunity status is a major factor in the development of HPV infection and consequent progression to HPV-related cancer (8). The cytokines in an immune-competent patient secreted by infected keratinocytes, such as transforming growth factor-β (TGF-β) and tumor necrosis factor-α (TNF-α) inhibit growth of HPV-16 and 18 and suppress E6 and E7, and so defeat HPV-related oncogenesis (9, 10). This process is not seen in an immune-compromised patient, such as an HIV patient or a patient that has undergone organ transplant. These patients will have HPV lesions, which might be benign warts or malignant neoplasms (8). In our case, the patient was immune compromised as a result of the long-term cyclosporine taking for heart transplant. Petel et al. reported that there is no difference in cancer differentiation between the immune compromised patients and the immune competent controls; however, the recurrence rate is much higher in the former (35% vs. 9%) (11). Mehard et al. found that one out of seven cases of PSCC in the oral cavity was positive for p16 (5). The present case showed some immunoreactivity to p16 which could suggest a possible role of HPV in the development of the tumor. However, in situ hybridization for selected low and high-risk types of HPV was negative. More case studies are needed to further evaluate the role of HPV in pathogensis of oral PSCC.
The prognosis of such lesion with this particular pathogenesis and location is uncertain. However, the presentation of the lesion with pedunculated nature and absence of muscular invasion could indicate favorable prognosis and the conventional TNM staging system might not be appropriate for this lesion. The clinical presentation of the current lesion resembles that of some pedunculated malignant colorectal polyps. The favorable prognostic factors in these polyps include pedunculated nature of the neoplasm, well or moderate differentiation of the neoplastic cells, absence of neural and vascular invasion, and completely resected tumor without marginal involvement. The tumor stage of the majority of pedunculated malignant colorectal polyps with favorable prognostic factors correspond to stage Tis (carcinoma in situ) and rarely to T1 in TNM system, and an endoscopically mucosal resection for these cases should be curable (12). All of these factors exist in the present tumor, which were treated by complete excision. In the three months follow up, the patient was doing well without any evidence of neoplasm or lymph node metastasis in physical and PET/CT examination. We therefore ask a question: Is it possible that oral pedunculated PSCC could also be staged with Tis to T1? To address this question, reports of many similar cases with follow up data are needed.
In summary, papillary squamous cell carcinoma is an uncommon form of oral squamous cell carcinoma which bears a favorable prognosis. Its most common sites are gingiva and buccal mucosa; however, it can occur in other locations, such as tip of the tongue, as reported in this case. It appears that an immune compromised status and existence of HPV in the tumor cells may contribute to the pathogenesis. However, more case studies are necessary to confirm the role of HPV in the pathogenesis of PSCC. The staging system of conventional SCC might not fit with the pedunculated PSCC; however, more case studies with long-term follow up are needed to achieve an accurate tumor stage and definite prognosis.
- Received May 1, 2018.
- Revision received May 19, 2018.
- Accepted May 22, 2018.
- Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved
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