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Spontaneous regression of advanced-stage oropharyngeal squamous cell carcinoma

Published online by Cambridge University Press:  13 October 2021

K L Lau Open the ORCID record for K L Lau [Opens in a new window] ,
C W Lee Open the ORCID record for C W Lee [Opens in a new window] ,
H Tustin  and
F Stafford
K L Lau*
Affiliation:
Department of Head and Neck Surgery, Sunderland Royal Hospital, Sunderland, UK
C W Lee
Affiliation:
Department of Head and Neck Surgery, Sunderland Royal Hospital, Sunderland, UK
H Tustin
Affiliation:
Department of Head and Neck Surgery, Sunderland Royal Hospital, Sunderland, UK
F Stafford
Affiliation:
Department of Head and Neck Surgery, Sunderland Royal Hospital, Sunderland, UK
*
Author for correspondence: Dr Kin Lun Lau, Department of Head and Neck Surgery, Sunderland Royal Hospital, Kayll Road, Sunderland SR4 7TP, UK E-mail: kennylau@doctors.org.uk
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Abstract

Background

Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour proven by microscopic examination in the absence of any substantial treatment. This paper presents the case of an older woman whose advanced-stage tonsillar squamous cell carcinoma was noted to have spontaneously regressed at seven months.

Case report

A 66-year-old woman presented with a 4-month history of dysphagia and odynophagia in September 2020. An exophytic tumour was seen on the right tonsil; this was diagnosed radiologically and histologically as a squamous cell carcinoma of the tonsils, with tumour–node–metastasis staging of T4aN0M0. The patient received best supportive care. Seven months later, the oropharyngeal lesion had disappeared, with no treatment. Subsequent computed tomography imaging showed radiological resolution of the previously noted right-sided oropharyngeal lesion.

Conclusion

Several mechanisms of spontaneous regression are discussed. Further studies should review this case in conjunction with other reports of spontaneous tumour regressions, to elucidate underlying mechanisms.

Keywords

Oropharyngeal CancerTonsillar CancerSquamous Cell CarcinomaSpontaneous Neoplasm Regression

Information

Type
Clinical Records
Information
The Journal of Laryngology & Otology , Volume 136 , Issue 9 , September 2022 , pp. 882 - 884
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press on behalf of J.L.O. (1984) LIMITED

Introduction

Spontaneous regression of cancer is a rare but recognised phenomenon in the literature. It is estimated to occur in 1 in every 140 000 cases, and is most commonly seen in melanoma, renal cell carcinoma and neuroblastoma cases.Reference Savarrio, Gibson, Dunlop, O'Rourke and Fitzsimons1 Spontaneous regression is defined as the partial or complete disappearance of a malignant tumour proven by microscopic examination in the absence of any substantial treatment.Reference Thomas and Badini2

Spontaneous regression of head and neck cancers has been reported previously, including in cases of lymphoma of the oral cavity,Reference Savarrio, Gibson, Dunlop, O'Rourke and Fitzsimons1 and squamous cell carcinoma (SCC) of the tongue,Reference Oya and Ikemura3 parotidReference Cuenca-Jimenez, Blanco-Guzman and Holwill4 and floor of the mouth.Reference de Andrade, Rena, Silva, Soares, Porcaro-Salles and Nunes5 This report presents the case of an older woman whose advanced-stage tonsillar SCC was noted to have spontaneously regressed at seven months. To our knowledge, this is the first reported case of spontaneous regression occurring in a case of SCC of the tonsils.

Case summary

A 66-year-old woman was referred to the head and neck team with a 4-month history of dysphagia and odynophagia in September 2020. She had a background of type 2 diabetes, spinal canal stenosis, alcoholic cirrhosis and osteoarthritis. An exophytic tumour was seen on the right tonsil, with extension to the soft palate and posteriolateral tongue.

Biopsies were taken under local anaesthetic and the tumour was histologically confirmed to be a human-papillomavirus-negative, moderately differentiated, keratinising SCC of tonsillar origin, with a tumour–node–metastasis (TNM) staging of T4aN0M0 (Figure 1).

Fig. 1.

Biopsy shows atypical infiltrative groups of squamous cells, some with keratinisation adjacent to a benign duct, in keeping with a squamous cell carcinoma of oropharyngeal origin. (H&E; ×200)

Computed tomography (CT) showed the lesion in the right tonsil extending through the superior constrictor to the parapharyngeal space, involving the right mandibular condyle, right lateral tongue and both sides of the soft palate (Figure 2).

Fig. 2.

Reconstructed axial computed tomography images of a mass lesion. (a) The soft tissue mass lesion is seen involving the right tonsil extending through the superior constrictor muscle to the parapharyngeal space. The right retromolar trigone, right mandibular condyle and posterior part of the right lateral border of the tongue are also involved. (b) There is radiological resolution of the previously observed right-sided oropharyngeal mass lesion. There is also partial healing of the previous right mandibular erosions, with a small residual defect seen in the right lingual cortex.

This case was discussed by the head and neck cancer multidisciplinary team. Considering the patient's functional status and co-morbidities, it was recommended that the patient receive best supportive care.

In April 2021, the patient was followed up in the head and neck clinic. Physical examination revealed that the oropharyngeal lesion had disappeared. Subsequent CT imaging showed radiological resolution of the previously noted right-sided oropharyngeal lesion, with no significant residual enhancement detected (Figure 2). There was also partial healing of the previously noted right-sided mandibular erosions. Given the patient's functional status and the absence of any tumour, a repeat biopsy was deemed inappropriate and was not performed. The patient is currently under follow up with the head and neck team.

Discussion

It is unclear what mechanisms are involved in spontaneous tumour regression. Studies have suggested that there is likely a complex interplay between a cytotoxic immune response against the tumour cells, terminal cell differentiation and apoptosis, among other theories.Reference Pakhmode6

Operative trauma has been suggested to enhance immunological resistance to tumour growth, and the removal of even parts of a tumour could facilitate destruction of the remaining tumour by the host immune system.Reference de Andrade, Rena, Silva, Soares, Porcaro-Salles and Nunes5 This theory is supported by cases in which spontaneously regressed Merkel cell carcinoma was shown to be infiltrated by clusters of differentiation 4+, 8+ and 3+ T lymphocytes after initial surgical biopsy.Reference Wooff, Trites, Walsh and Bullock7 Spontaneous regression has been observed to occur from two weeks to five months after the initial biopsy.Reference Moghaddam P, Cornejo, Hutchinson, Tomaszewicz, Dresser and Deng8 In our patient, five biopsies were taken and spontaneous regression was observed six months later. It is possible that mechanical trauma such as a biopsy can induce an anti-tumoural T-cell response, and result in T-cell mediated apoptotic cell death.

The most frequently reported symptom in cases of spontaneous tumour regression is a preceding acute febrile episode, secondary to either a natural infection or vaccination therapy.Reference Thomas and Badini2 A hyperthermal state may be able to stimulate dendritic cells, enhance antigen presentation and activate a humoral immune response against tumour cells.Reference Hobohm9 Cancer cells have also been shown to be more susceptible to heat than normal cells and undergo more extensive necrosis in vitro.Reference Trieb, Sztankay, Amberger, Lechner and Grubeck-Loebenstein10 Our patient did not experience any significant infections during the six months between diagnosis and regression. However, as part of the national coronavirus disease 2019 vaccination programme, she received two doses of AstraZeneca vaccines at two months and five months respectively. As fever is a common side effect of the vaccine, it is possible that the patient did experience a febrile episode leading up to the spontaneous tumour regression.

The authors have also considered the possibility of misdiagnosis. Notably, keratoacanthoma of the oral cavity is clinically very similar to a well-differentiated SCC.Reference Chen, Lin, Lin and Chen11 However, intra-oral keratoacanthomas are rare as they most commonly arise from sun-exposed surfaces. Histologically, the hallmarks of a central keratin-filled crater and bland squamous cells in keratoacanthoma were also absent in our case.Reference Zargaran and Baghaei12 The lack of pseudosarcomatous spindle cell proliferation also excluded the diagnosis of an intra-oral inflammatory pseudotumour.Reference Earl, Lowry and Sloan13 Our biopsy showed a heavily inflamed, disorganised, infiltrative lesion, with marked nuclear atypia and keratinisation of the deeper aspects, which is diagnostic for genuine invasion in dysplastic squamous lesions (Figure 1).

  • • Spontaneous regression of cancer is a rare but recognised phenomenon

  • • This paper reports spontaneous regression of tonsillar squamous cell carcinoma

  • • Mechanical trauma such as biopsy may induce an anti-tumoural T-cell response and result in T-cell mediated apoptotic cell death

  • • A hyperthermal state secondary to a natural infection or vaccination therapy may stimulate dendritic cells, enhance antigen presentation and activate a humoral immune response against tumour cells

This paper reports a case of spontaneous regression of a stage 4 oropharyngeal SCC of tonsillar origin. Further studies should review our case in conjunction with other reports of spontaneous tumour regression, to elucidate underlying mechanisms and potential novel treatments.

Competing interests

None declared

Footnotes

Dr K L Lau takes responsibility for the integrity of the content of the paper

References

Savarrio, L, Gibson, J, Dunlop, DJ, O'Rourke, N, Fitzsimons, EJ. Spontaneous regression of an anaplastic large cell lymphoma in the oral cavity: first reported case and review of the literature. Oral Oncol 1999;35:609–13CrossRefGoogle ScholarPubMed
Thomas, JA, Badini, M. The role of innate immunity in spontaneous regression of cancer. Indian J Cancer 2011;48:246–51CrossRefGoogle ScholarPubMed
Oya, R, Ikemura, K. Spontaneous regression of recurrent squamous cell carcinoma of the tongue. Int J Clin Oncol 2004;9:339–42CrossRefGoogle ScholarPubMed
Cuenca-Jimenez, T, Blanco-Guzman, M, Holwill, S. Case report: extensive spontaneous regression of metastatic parotid keratinizing squamous cell carcinoma. Br J Oral Maxillofac Surg 2015;53:e48–9CrossRefGoogle Scholar
de Andrade, Sousa A, Rena, RL, Silva, GS, Soares, JMA, Porcaro-Salles, JM, Nunes, L et al. Spontaneous remission of a squamous cell carcinoma of the floor of the mouth. J Craniomaxillofac Surg 2014;42:1536–9CrossRefGoogle Scholar
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Wooff, JC, Trites, JR, Walsh, NMG, Bullock, MJ. Complete spontaneous regression of metastatic Merkel cell carcinoma: a case report and review of the literature. Am J Dermatopathol 2010;32:614–17CrossRefGoogle ScholarPubMed
Moghaddam P, Ahmadi, Cornejo, KM, Hutchinson, L, Tomaszewicz, K, Dresser, K, Deng, A et al. Complete spontaneous regression of Merkel cell carcinoma after biopsy: a case report and review of the literature. Am J Dermatopathol 2016;38:e154–8CrossRefGoogle Scholar
Hobohm, U. Fever and cancer in perspective. Cancer Immunol Immunother 2001;50:391–6CrossRefGoogle Scholar
Trieb, K, Sztankay, A, Amberger, A, Lechner, H, Grubeck-Loebenstein, B. Hyperthermia inhibits proliferation and stimulates the expression of differentiation markers in cultured thyroid carcinoma cells. Cancer Lett 1994;87:65–71CrossRefGoogle ScholarPubMed
Chen, Y-K, Lin, L-M, Lin, C-C, Chen, C-H. Keratoacanthoma of the tongue: a diagnostic problem. Otolaryngol Head Neck Surg 2003;128:581–2CrossRefGoogle Scholar
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Figure 0

Fig. 1. Biopsy shows atypical infiltrative groups of squamous cells, some with keratinisation adjacent to a benign duct, in keeping with a squamous cell carcinoma of oropharyngeal origin. (H&E; ×200)

Figure 1

Fig. 2. Reconstructed axial computed tomography images of a mass lesion. (a) The soft tissue mass lesion is seen involving the right tonsil extending through the superior constrictor muscle to the parapharyngeal space. The right retromolar trigone, right mandibular condyle and posterior part of the right lateral border of the tongue are also involved. (b) There is radiological resolution of the previously observed right-sided oropharyngeal mass lesion. There is also partial healing of the previous right mandibular erosions, with a small residual defect seen in the right lingual cortex.