Metastatic Lung Cancer to the Head and Neck: A Clinico-Pathological Study on 21 Cases with Narrative Review of the Literature

Abstract

Metastases from lung cancer to the oral cavity and to the head and neck generally are very infrequent and usually manifest in advanced stages of the disease. Even more rarely, they are the first sign of an unknown metastatic disease. Nevertheless, their occurrence always represents a challenging situation both for clinicians, in the management of very unusual lesions, and for pathologists, in the recognition of the primary site. We retrospectively studied 21 cases of metastases to the head and neck from lung cancer (sixteen males and five females, age range 43-80 years; eight cases localized to the gingiva [two of these to the peri-implant gingiva], seven to the sub-mandibular lymph nodes, two to the mandible, three to the tongue, one case to the parotid gland; in eight patients, metastasis was the first clinical manifestation of an occult lung cancer) and proposed a wide immunohistochemical panel for a proper identification of the primary tumor histotype, including CK5/6, CK8/18, CK7, CK20, p40, p63, TTF-1, CDX2, Chromogranin A, Synaptophysin, GATA-3, Estrogen Receptors, PAX8, PSA. Furthermore, we collected data from previously published studies and narratively reviewed the relevant literature.

Keywords: head and neck metastasis; immunohistochemistry; lung cancer; metastatic lung cancer; oral cavity; oral metastasis.

Figure 1

Swelling of the retromolar trigone covered by normally colored mucosa (A) with infiltration of the underlining bone (B), diagnosed as metastasis from LC (C).

Figure 2

Wide ulcerated lesion of the adherent maxillary gingiva extended to the palate and the cheek mucosa (A), associated with a residual decayed dental root (B); the lesion was removed (C) to improve function and finally resulted as the first manifestation of an unknown non-small cell lung carcinoma (D).

Figure 3

Gingival reddish enlargement involving the 3.2, 3.3 and 3.4 (A) with alveolar bone involvement, (B) mimicking a periodontal lesion but unresponsive to the conventional procedure of dental hygiene and full mouth disinfection, thus needing a biopsy sampling; the histological diagnosis revealed it as the first manifestation of an unknown adenocarcinoma of pulmonary origin.

Figure 4

Metastatic lesion of the tongue (A) occurring in a patient already diagnosed with small cell carcinoma of the lung, as evident in PET scan (B), and with simultaneous brain metastasis (C).

Figure 5

Non−specific parotid enlargement (A) occurring in a patient with an unknown small cell lung carcinoma, subsequently detected during the clinical work−up for the primitive tumor identification (B).

Figure 6

(A) Histological image of an intraosseous metastasis from lung adenocarcinoma, showing bone fragments (b) intermingled with groups of neoplastic cells (arrows) [100×, H.E.]; (B) Oral submucosal infiltration of malignant poorly formed glands [100×, H.E.]; (C) Immunohistochemical staining showing CK7 positivity in neoplastic glands [50×, H.E.]; (D) Immunohistochemistry reveals positivity for TTF-1 in neoplastic cells, suggesting lung origin [50×, H.E.].