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Posterior Subglottic Mass in a Patient With a History of Rectal Adenocarcinoma and Lung Metastases

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

The patient is a 48-year-old man with a history of a rectal adenocarcinoma (cT3N2bM0) diagnosed 9 years prior. Following neoadjuvant chemoradiotherapy, low anterior resection, and 6 cycles of adjuvant FOLFOX therapy (fluorouracil, leucovorin, and oxaliplatin), he had developed a lung metastasis (KRAS wild type) 1 year later. He subsequently developed multiple lung metastases treated with palliative local interventions (lobectomy, radiofrequency ablation) and 4 lines of chemotherapy. Owing to symptomatic lung disease, he was enrolled in a clinical trial (NCT03502733) following informed consent and achieved a confirmed partial response. After 9 months, contrast computed tomography restaging scans noted a new, 1-cm posterior subglottic lesion of unclear origin (Figure, A). He had no shortness of breath or noisy breathing, dysphagia, voice change, or hemoptysis. A partial response was maintained without evidence of progression of lung disease.

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B. Metastatic rectal adenocarcinoma

Subglottic malignant neoplasm is rare. In a large review of 160 000 laryngeal squamous cell carcinomas, 2% were in the subglottis.1 Even rarer is the rate of metastatic lesions to the larynx from other primary sites, comprising 0.09% to 0.4% of laryngeal tumors.2 A literature review performed by Zenga et al3 in 2016 identified 41 cases of metastatic spread to the larynx from various primary tumor sites, the most common of which was colorectal adenocarcinoma (24%) followed by renal cell carcinoma (15%) and prostate carcinoma (15%).

This patient’s biopsy specimen was identified as a colorectal adenocarcinoma metastasis based on the characteristic appearance of tubular glandular tissue within a stromal matrix on hematoxylin-eosin staining and immunohistochemical staining for CDX2. A transcription factor within the nucleus, CDX2 is a marker for enteric (intestinal) differentiation and is identifiable via immunohistochemistry in greater than 90% of intestinal adenocarcinomas.4 Oncomine Comprehensive Assay v3 (Thermo Fisher) revealed a pathogenic NRAS (c.182A>G) and TP53 (c.673-1G>A) variation. Mismatch repair protein expression was intact, and the specimen was negative for ERBB2 amplification.

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Article Information

Corresponding Author: Clint T. Allen, MD, Otolaryngology Consultation Service, National Institute on Deafness and Other Communication Disorders, National Institutes of Health, Bldg 10, Room 7N240C, Bethesda, MD 20892 (clint.allen@nih.gov).

Published Online: September 10, 2020. doi:10.1001/jamaoncol.2020.2693

Conflict of Interest Disclosures: None reported.

Funding/Support: This work was supported by the Intramural Research Program of the National Institutes of Health, National Institute on Deafness and Other Communication Disorders, project No. ZIA-DC00008.

Role of the Funder/Sponsor: The National Institute on Deafness and Other Communication Disorders had no role in the preparation of or decision to submit this manuscript but did approve the final version of the manuscript.

Additional Contributions: We thank the patient for granting permission to publish this information.

References
1.
Hoffman  HT , Porter  K , Karnell  LH ,  et al.  Laryngeal cancer in the United States: changes in demographics, patterns of care, and survival.   Laryngoscope. 2006;116(9 Pt 2)(suppl 111):1-13. doi:10.1097/01.mlg.0000236095.97947.26PubMedGoogle ScholarCrossref
2.
Flint  P , Cummings  C .  Cummings Otolaryngology. 6th ed. Elsevier, Saunders; 2015:1601-1633.
3.
Zenga  J , Mehrad  M , Bradley  JP .  Metastatic cancer to the larynx: a case report and update.   J Voice. 2016;30(6):774.e9-774.e12. doi:10.1016/j.jvoice.2015.11.017PubMedGoogle ScholarCrossref
4.
Fleming  M , Ravula  S , Tatishchev  SF , Wang  HL .  Colorectal carcinoma: pathologic aspects.   J Gastrointest Oncol. 2012;3(3):153-173. doi:10.3978/j.issn.2078-6891.2012.030PubMedGoogle Scholar
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