Abstract
Data regarding the development of head and neck metastases are limited, with the majority of the studies focusing on single cases affecting mainly the oral cavity and surrounding tissues. This study describes the incidence of head and neck metastases from primary tumours originating elsewhere. The medical records of selected patients were reviewed, and socio-demographic data as well as information about the localization of the primary tumours and their metastases to this region, treatment modalities employed, follow-up, and outcomes were collected. A total of 24 cases were found. The mean age at diagnosis was 52.1 ± 17.6 years and the male to female ratio was 1:1.4. Most primary tumours were located in the lung and breast. The overall 1-, 2-, and 5-year survival rates were 63.0%, 39.1%, and 19.6%, respectively. Radiotherapy for the metastatic focus significantly prolonged the survival time of the patients ( P = 0.048). Cervical lymph node metastases are a common event in patients with primary tumours growing elsewhere.
An experienced oral pathologist will examine a number of biopsy samples taken from tumoral lesions affecting the head and neck region; these are normally expected to be squamous cell carcinoma, the most frequent malignant lesion in this region. During the microscopic examination, the pathologist may discover a tumoral lesion, the morphology of which is believed to be metastatic, originating from a primary tumour growing at a distant site. Even taking into consideration the rarity of this diagnosis and its challenges, an experienced pathologist should make an appropriate diagnosis of the metastatic lesion, since its presence in this region appears to have a high impact on the prognosis and survival time of the patient.
It is know that 1% of all head and neck malignancies are metastases of primary tumours developing elsewhere. However, one study that investigated the incidence of oral and craniofacial metastases found 2.39% of lesions were metastases, indicating that their occurrence in this region may be much higher than expected. These discrepancies could be explained by a number of factors, but one that is very important is the number of patients included in each study. Moreover, there have been few reports evaluating the incidence of metastases with regards to all regions of the head and neck, such as cervical lymph nodes, salivary glands, and thyroid, and the majority of studies have focused particularly on the incidence of oral soft tissue or jawbone metastases.
Given the rarity of this condition, the mechanism leading to the occurrence of head and neck metastases from primary tumours developing at distant sites is still unknown. Additionally, information is scarce on their predilection for specific sites in this anatomic region, clinical–demographic data of the affected patients, primary tumour types that frequently give rise to metastases in this area, the best treatment option to control them, and their impact on the prognosis, as well as on the survival rate. Moreover, this information has normally come from single case reports and/or small series. Bearing in mind this gap in the literature, especially the lack of studies aimed at helping clinicians to predict the areas at higher risk of metastases in patients with a history of cancer, the purpose of this study was to describe the clinico-pathological features, treatment, and outcomes of metastatic lesions in a cohort from Brazil.
Patients and methods
This retrospective study was conducted based on the medical records of patients who developed metastatic lesions in the head and neck region between 1990 and 2011. The main eligibility criteria for including metastatic patients in the current study were their classification according to the International Classification of Diseases, Tenth Revision (ICD-10) codes C76.0 (malignant neoplasm of other and ill-defined sites located in the head, face, and neck) and C77.0 (secondary and unspecified malignant neoplasm of the lymph nodes located in lymph nodes of head, face, and neck) and the presence of data in the medical records, such as a histopathological exam and/or a conventional X-ray/computed tomography/magnetic resonance imaging scan, suggestive of a metastatic lesion. To confirm the diagnosis, all slides from the metastatic lesions and primary tumours of each patient were gathered and reviewed by three investigators (AML, PRF, SVC).
The following information was collected for the patients enrolled: socio-demographic data, localization of the metastatic lesions and primary tumours, treatment used to control the two lesions, follow-up, and outcomes. This study was reviewed and approved by the institutional committee for ethics in research.
The statistical analysis was performed using SPSS software v. 17.0 (SPSS Inc., Chicago, IL, USA). Only the overall mortality was analyzed. Overall survival curves for different clinico-pathological factors were obtained using the Kaplan–Meier method and compared by a univariate approach (log-rank test). A P -value of 0.05 or less was considered as statistically significant.
Results
A total of 2500 cases of head and neck malignancies were identified. Of these, 24 cases corresponded to patients who developed head and neck metastases from primary tumours growing at a distant site, representing 0.96% of all head and neck malignancies. Ten of the patients were males and 14 were females. The mean age of the patients at diagnosis was 52.1 ± 17.6 years, with the peak incidence during the sixth decade of life. The metastasis appeared to occur earlier in females (45.6 years) than in males (61.1 years). Of the 24 cases, 17 (70.8%) developed cervical lymph node metastases, with the majority involving levels IV and V (9/17, 52.9%). In eight of the 24 patients (33.3%), other regions were affected, such as the maxillary sinus (one case; Ewing’s sarcoma), gingiva (three cases; adenocarcinoma, squamous cell carcinoma, and urothelial carcinoma), parotid gland (one case; melanoma), mandible (two cases; neuroblastoma and polymorphous low-grade adenocarcinoma (PLGA)), and thyroid (one case; large cell carcinoma). Only one patient presented synchronic head and neck metastases, with one focus occurring in the lymph node and one in the gingiva.
In our casuistic study, metastatic lesions originating from the lung were seen in six patients (25%); the lungs represented the main location of primary tumours in the present study. The next most frequent primary tumour location was the breast (three cases, 12.5%), followed by the liver, pancreas, and prostate (two cases each, 8.3%). Maxillary sinus, skin, urethra, ovary, mediastinum, adrenal gland, oesophagus, intestine, and bone were the primary site in single cases (each 4.2%). Analyzing the data on the main location of the primary tumours with respect to gender, it was found that, for women, the breast was the most common site (three cases, 21.4%), while for men, it was the lung (four cases, 40%).
Histological analysis showed a high frequency of carcinomas (20 cases, 83.3%). Other histological types found were Ewing’s sarcoma, melanoma, neuroblastoma, and pheochromocytoma, with one case each. Eight patients (33.3%) were treated for both the primary tumour and metastatic lesions, 14 patients (58.3%) received treatment for only the primary tumour or the metastatic lesion, and two patients (8.3%) did not receive any modalities of treatment due to the advanced disease stage – they were forwarded to palliative care. Surgery and surgery + adjuvant therapies were the most common approaches used to treat the primary tumours (10 cases, 41.7%), while radiotherapy was the most used modality in the treatment of metastatic lesions (15 cases, 62.5%).
Local swelling was the most common symptom found. Other symptoms such as pain, paresthesia, and bleeding were also reported, but at lower frequencies. Approximately 40% of patients (nine cases) were identified as having developed secondary metastatic foci, with the liver the most common location (four cases, 44.4%). Of the 24 cases, 17 (70.8%) had head and neck metastases as the first clinical manifestation of their conditions. Of these, two patients (11.8%) were considered out of therapeutic possibilities at the first appointment. Further, five patients (35.7%) who had not developed metastatic lesions at the time of the diagnosis had done so by the third year of follow-up. For some lesions (cases 2, 16, 17, and 18, Table 1 ), the hypothesis of secondary synchronous and/or metachronous tumour was raised, which is discussed further below.
| Case | Gender/age, years | Primary tumour localization | Histology | Treatment of primary tumor a | Site of HNM b | Occurrence of HNM after initial diagnosis | Treatment of HNM a | Follow-up after HNM, months | Outcome c |
|---|---|---|---|---|---|---|---|---|---|
| 1 | M/51 | Adrenal gland | Pheochromocytoma | S + Rt + ChT | CLN (−) | First clinical manifestation | No | 48 | DOD |
| 2 | F/19 | Bone–rib | Ewing’s sarcoma | S + Rt + ChT | Maxillary sinus | 22 months | No | 13 | DOD |
| 3 | F/66 | Breast | Invasive ductal carcinoma | S + Rt + ChT | CLN (level IV and V) | 21 months | Rt | 7 | AWD |
| 4 | F/70 | Breast | Invasive ductal carcinoma | ChT | CLN (level IV and V) | First clinical manifestation | No | 3 | DOD |
| 5 | F/68 | Breast | Invasive ductal carcinoma | S + Rt + ChT | CLN (level IV and V) | 10 months | Rt | 6 | DOD |
| 6 | F/61 | Oesophagus | Adenocarcinoma | S + Rt | CLN (level II and III) | First clinical manifestation | S + Rt | 114 | DOD |
| 7 | F/47 | Intestine | Mucinous adenocarcinoma | No | Gingiva | First clinical manifestation | Rt | 10 | AWD |
| 8 | M/50 | Liver | Hepatocellular carcinoma | No | CLN (−) | First clinical manifestation | Rt | 2 | AWD |
| 9 | M/54 | Liver | Hepatocellular carcinoma | No | CLN (level III) | First clinical manifestation | Rt + ChT | 4 | DOD |
| 10 | M/51 | Lungs | Adenocarcinoma NOS | No | CLN (level IV and V) | First clinical manifestation | No | 10 | DOD |
| 11 | M/60 | Lungs | Squamous cell carcinoma | Rt + ChT | CLN (level IV and V) | First clinical manifestation | No | 3 | DOD |
| 12 | F/38 | Lungs | Adenocarcinoma NOS | ChT | CLN (−) | First clinical manifestation | No | 2 | DOD |
| 13 | F/59 | Lungs | Large cell carcinoma | Rt + ChT | CLN (level V) | First clinical manifestation | No | 2 | DOD |
| 14 | M/63 | Lungs | Large cell carcinoma | No | Thyroid | First clinical manifestation | S + Rt | 123 | AWD |
| 15 | M/51 | Lungs | Adenocarcinoma NOS | No | CLN (level V) | First clinical manifestation | Rt + ChT | 14 | DOD |
| 16 | F/40 | Maxillary sinus | PLGA | S | Anterior mandible | 144 months | S + Rt | 11 | AWD |
| 17 | F/5 | Mediastinum | Neuroblastoma | S + Rt + ChT | Mandible | 6 months | Rt | 40 | DOD |
| 18 | F/38 | Ovary | Squamous cell carcinoma | No | Gingiva | First clinical manifestation | No | – | – |
| 19 | F/59 | Pancreas | Ductal adenocarcinoma | No | CLN (level III–V) | First clinical manifestation | Rt + ChT | 7 | DOD |
| 20 | F/46 | Pancreas | Ductal adenocarcinoma | No | CLN (−) | First clinical manifestation | Rt + ChT | 39 | DOD |
| 21 | M/77 | Prostate | Acinic cell adenocarcinoma | S + Rt | CLN (level III) | 36 months | Rt | 72 | NED |
| 22 | M/78 | Prostate | Acinic cell adenocarcinoma | ChT | CLN (level IV and V) | First clinical manifestation | Rt | 16 | DOD |
| 23 | M/76 | Skin (nose wing) | Melanoma | S | Parotid gland | 35 months | S + Rt | 23 | DOD |
| 24 | F/43 | Urethra | Urothelial carcinoma | S | CLN (level I)/gingiva | First clinical manifestation | No | 16 | AWD |
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