A 68-year-old man with a long history of using chewing tobacco comes to the office for follow up of squamous cell carcinoma (SCC) of the oral cavity. A month ago, the patient was diagnosed with SCC of the left lateral tongue. He underwent resection, the surgical specimen showed clear margins, and he started additional treatment. The patient recently noticed a second ulcerative lesion on the right lateral tongue. Biopsy is performed and it also shows SCC. The second tumor most likely arose from which of the following mechanisms?

Question

A 68-year-old man with a long history of using chewing tobacco comes to the office for follow up of squamous cell carcinoma (SCC) of the oral cavity.  A month ago, the patient was diagnosed with SCC of the left lateral tongue.  He underwent resection, the surgical specimen showed clear margins, and he started additional treatment.  The patient recently noticed a second ulcerative lesion on the right lateral tongue.  Biopsy is performed and it also shows SCC.  The second tumor most likely arose from which of the following mechanisms?

Quizplus · Accepted Answer

This patient with mucosal head and neck squamous cell carcinoma (HNSCC) has developed a second primary tumor, which is common with HNSCC due to field cancerization. Field cancerization describes a large area of cells within a field (eg, upper aerodigestive tract) that are "primed" to develop cancer because of widespread exposure to mutagens (eg, tobacco). Mutations that affect many similar cells can increase the likelihood of developing multiple primary malignancies, analogous to germline mutations in tumor suppressor genes (eg, BRCA1 or BRCA2 in breast and ovarian cancer). Field cancerization likely underlies the development of many common cancers, including: Even with adequate treatment of a malignancy, the areas affected by field cancerization remain at higher risk of developing multiple primary malignancies, as seen in this patient. Therefore, patients diagnosed with any of these cancers require comprehensive evaluation and continued surveillance of the at-risk area (eg, colonoscopy, comprehensive skin examination, panendoscopy of the upper aerodigestive tract). (Choice A) Chemotherapy can induce secondary malignancies, most commonly leukemia and lymphoma, in cancer survivors. In contrast to the tumors in this patient, secondary malignancies are seen years or even decades later. (Choices C and F) Most carcinomas, including HNSCC, spread via the lymphatic system, leading to metastases in the regional (eg, ipsilateral anterior neck) lymph nodes. However, it is unlikely for the carcinoma to spread back up to a contralateral epithelial site. Hematogenous spread is less common with carcinomas and typically results in metastases to distant sites. (Choice D) Certain anatomic sites (eg, eyes, testes) display inherent immune privilege, in which foreign grafts or cancers that would otherwise induce immunologic rejection are tolerated. Cancers may establish local sites of immune privilege to evade destruction, but this does not cause new tumor formation. (Choice E) Cancer treatment (eg, chemotherapy, radiation therapy) can result in impaired wound healing, which can result in acutely ulcerative oral lesions due to mucositis. However, these lesions would not be malignant. Educational objective: Field cancerization can occur when a large area of cells is exposed to carcinogens that induce mutations, leading to a higher risk of forming cancers. __________ References: An evolutionary perspective on field cancerization. (http://www.ncbi.nlm.nih.gov/pubmed/29217838) Wound healing and cancer stem cells: inflammation as a driver of treatment resistance in breast cancer. (http://www.ncbi.nlm.nih.gov/pubmed/25674014) Epithelial stem cells, wound healing and cancer. (http://www.ncbi.nlm.nih.gov/pubmed/22362215)

A 68-Year-Old Man with a Long History of Using Chewing