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Dermatology

Lip Squamous Cell Carcinoma With Spontaneous Eruption and Drainage

Educational Objective
Based on this clinical scenario and the accompanying image, understand how to arrive at a correct diagnosis.

1 Credit CME

JAMA Otolaryngology–Head & Neck Surgery

Published Online: February 2, 2023

Clinical Challenge

Article Information and Disclosures

Tiffany Toni, BS¹;

Clint T. Allen, MD¹;

Wojciech K. Mydlarz, MD²

Author Affiliations

¹Section on Translational Tumor Immunology, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bethesda, Maryland
²Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, Maryland

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A 69-year-old woman with a newly diagnosed T3N2cM0 poorly differentiated squamous cell carcinoma unrelated to human papillomavirus (HPV) of the lower lip mucosa presented to the medical oncology clinic 3 days after initiating neoadjuvant immune checkpoint blockade immunotherapy with redness and swelling of the tumor site. Four days after treatment, a white head formed overlying the tumor that erupted through the skin surface (Figure 1). Thin, cloudy discharge that was not foul-smelling drained from the tumor from posttreatment days 5 to 10, at which point the drainage stopped spontaneously. Throughout, the patient reported no pain and remained afebrile. Laboratory results on days 5, 9, and 14 demonstrated the absence of leukocytosis, and serial wound cultures failed to demonstrate pathogenic growth. No antibiotics were administered. The patient completed the neoadjuvant immunotherapy and underwent a margin-negative tumor resection without intraoperative or postoperative complications.

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B. Immunotherapy-related inflammation

Tumor liquification possibly resulting from rapid necrosis of the tumor during immunotherapy can represent a positive response to treatment and immunotherapy-associated tumor death. Although unknown at the time, retrospective study of this patient’s surgical specimen revealed evidence of pathologic response with a substantial degree of tumor necrosis and viable primary tumor regression of 20% within the fibrotic tumor bed (Figure 2).¹^,2 Histologic analysis of the resected primary tumor specimen also revealed evidence of heavy immune infiltrate distributed throughout the tumor. Interestingly, this patient was clinically classified with N2c disease at the time of diagnosis based on positron emission and contrast-enhanced computed tomography imaging but was found to be pathologically N0 upon analysis of her surgical specimen.¹ Such data indicate that immune checkpoint blockade–based neoadjuvant immunotherapy may result in significant pathologic responses prior to surgery in both the primary tumor and regional lymph node metastases.

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Article Information

Corresponding Author: Wojciech K. Mydlarz, MD, Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins University School of Medicine, JHOC 6210, 601 N Caroline St, Baltimore, MD 21287 (mydlarz@jhmi.edu).

Published Online: February 2, 2023. doi:10.1001/jamaoto.2022.4828

Conflict of Interest Disclosures: Dr Toni reported involvement with a Medical Research Scholars Program fellowship from the National Institutes of Health (NIH) during the submitted work. No other disclosures were reported.

Additional Contributions: We thank Chyi-Chia Richard Lee, MD, PhD, for his evaluation of the pathology specimen and critical review of the manuscript. This individual was not compensated for their contributions. We also thank the patient for granting permission to publish this information.

Additional Information: This research was made possible through the NIH Medical Research Scholars Program, a public-private partnership supported jointly by the NIH and contributions to the Foundation for the NIH from the Doris Duke Charitable Foundation, the American Association for Dental Research, the Colgate-Palmolive Company, and other private donors. For a complete list, please visit the Foundation website at http://fnih.org/what-we-do/current-education-and-training-programs/mrsp.

References

Redman JM , Friedman J , Robbins Y , et al. Enhanced neoepitope-specific immunity following neoadjuvant PD-L1 and TGF-β blockade in HPV-unrelated head and neck cancer. J Clin Invest. 2022;132(18):e161400. doi:10.1172/JCI161400 Google Scholar Crossref

Stein JE , Lipson EJ , Cottrell TR , et al. Pan-tumor pathologic scoring of response to PD-(L)1 blockade. Clin Cancer Res. 2020;26(3):545-551. doi:10.1158/1078-0432.CCR-19-2379 PubMed Google Scholar Crossref

Shibata H , Saito S , Uppaluri R . Immunotherapy for head and neck cancer: a paradigm shift from induction chemotherapy to neoadjuvant immunotherapy. Front Oncol. 2021;11:727433. doi:10.3389/fonc.2021.727433 PubMed Google Scholar Crossref

Merck Sharp & Dohme LLC. Study of pembrolizumab given prior to surgery and in combination with radiotherapy given post-surgery for advanced head and neck squamous cell carcinoma (MK-3475-689). Updated December 2022. https://clinicaltrials.gov/ct2/show/NCT03765918

Chiou VL , Burotto M . Pseudoprogression and immune-related response in solid tumors. J Clin Oncol. 2015;33(31):3541-3543. doi:10.1200/JCO.2015.61.6870 PubMed Google Scholar Crossref

AMA CME Accreditation Information

Credit Designation Statement: The American Medical Association designates this Journal-based CME activity activity for a maximum of 1.00  AMA PRA Category 1 Credit(s)™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to:

1.00 Medical Knowledge MOC points in the American Board of Internal Medicine's (ABIM) Maintenance of Certification (MOC) program;;
1.00 Self-Assessment points in the American Board of Otolaryngology – Head and Neck Surgery’s (ABOHNS) Continuing Certification program;
1.00 MOC points in the American Board of Pediatrics’ (ABP) Maintenance of Certification (MOC) program;
1.00 Lifelong Learning points in the American Board of Pathology’s (ABPath) Continuing Certification program; and
1.00 CME points in the American Board of Surgery’s (ABS) Continuing Certification program

It is the CME activity provider's responsibility to submit participant completion information to ACCME for the purpose of granting MOC credit.