Case Presentation: A 63 year-old man with a history of tobacco abuse presented with progressive left-sided neck pain radiating down the left arm with associated weakness, neck swelling, low-grade fevers, and unintentional weight loss. Nine months prior to this presentation, the patient had a C3-5 anterior cervical decompression and fusion (ACDF) to address similar symptoms. Cervical MRI prior to surgery noted degenerative disc disease, neural foramen narrowing, and unremarkable paraspinal muscles and cervical soft tissue. On exam, a firm, non-mobile, tender mass was palpated on the left neck. CT imaging revealed a 6 x 6 x 4 cm heterogenous tumor with adjacent C3-5 bony destruction, spinal canal and neurovascular invasion, and an enlarged level 5 lymph node. Additional metastatic work-up revealed a 1.3 cm right lung nodule and a 5 cm posterior soft tissue mass with left 6th and 7th rib destruction. Biopsy demonstrated a poorly-differentiated carcinoma with glandular features. No site of origin could be determined. Biopsy of the lung nodule revealed a poorly-differentiated carcinoma favoring squamous differentiation. Despite extensive histopathologic staining, the primary cell lineage of both the lung nodule and the neck mass could not be determined. The conclusion was that the patient either had a metastatic carcinoma with divergent differentiation (squamous and glandular) or two synchronous primary tumors. He received palliative radiation to the neck and subsequent chemotherapy for adenocarcinoma of unknown primary.
Discussion: Asymptomatic dormant micrometastases are metastatic tumor cells that can persist in the body for years. This phenomenon is limited in part due to a lack of vascularization of the tumor cell microenvironment. So-called angiogenic/tumor mass dormancy is characterized by 1-2mm avascular micrometastases. Tumor-associated macrophages, inflammatory mediators, and even the coagulation system likely play a role in metastatic outgrowth. An association between primary tumor resection and an early peak of metastatic recurrence 8-12 months later has been observed in multiple cancer types, typically in breast cancer. A similar phenomena has been observed in patients undergoing resection of non-small cell lung cancer, with an early peak in distant metastases detected approximately 9 months surgery. The hypothesized mediators of surgery-driven metastatic outgrowth include increased levels of circulating VEGF following surgery, as well as the disruption of the tumor-host interactions that play a role in maintaining tumor dormancy. Our hypothesis in this case is that similar mechanisms provoked by elective ACDF promoted local angiogenesis and ultimately metastatic outgrowth of a previously dormant tumor micrometastasis.
This case also raises the question of whether patients should be advised to completed age and gender-appropriate cancer screening prior to elective surgery. Current guidelines recommend that this patient have undergone annual low-dose CT scans given his risk for lung cancer. This screen may have resulted in earlier detection of a primary malignancy, Future research is needed to definitively establish causation between elective surgery and progression of concurrent malignancy, as well as to determine whether current screening provide any degree of harm reduction.
Conclusions: This case highlights the potential for surgery-driven growth of tumor cells and suggests the need for consideration of cancer screening prior to elective surgery.