Pattern and Outcome of Metastatic Malignant Lesions to the Jaws: A Systematic Review of 594 Cases

Abstract

The jaws are affected secondarily by metastasis from a distant site. Metastatic lesions of jaws are very rare and constitute about 1% of all the malignancies occurring in the jaw, and the pattern of metastasis differs by age and sex. The objective of this review was to analyze the pattern of metastatic jaw lesions and its outcome. This was a systematic review of cases of metastatic jaw lesions published between 1950 and 2022. An electronic search of PubMed, Scopus, Web of Science, African Journals Online, and Google Scholar was performed. Only case reports or case series with histopathological results demonstrating metastasis to the jaws were included. The main outcomes included demographics, primary site, metastatic site, clinical manifestations, and patient survival. Descriptive and multivariate analysis and a Kaplan-Meier survival curve were performed. A total of 450 articles were selected with a total of 594 cases. The mean age of the patients was 54.31 (SD = 19.49) years with a median age of 58 (IQR = 47–68) years. There were slightly more females (N = 299, 50.3%) with a male-to-female ratio of 1:1.01. The most common malignant lesion to metastasize to the jaws was adenocarcinoma (N = 230, 38.7%). In females, the frequent sites of the primary lesion were the breast (N = 99, 33.1%), thyroid (N = 52, 17.4%), and lungs (N = 27, 9.0%), whereas in males they were the lung (N = 57, 19.3%) the prostate (N = 41, 13.9%), liver (N = 36, 12.2%), and kidney (N = 28, 9.5%). The frequently reported clinical symptoms include jaw swelling (N = 460, 77.4%), pain (N = 250, 42.1%), paresthesia (N = 117, 29.8%), and trismus (N = 72, 12.1%). Regarding the outcome, 65.3% had succumbed to the disease at the time of publication of their cases. The survival of patients with metastatic jaw lesions did not depend on the demographics of the patient, the primary site, and the treatment of the primary lesion. Metastasis to the jaw bone is very rare and its prognosis is poor. Females and the elderly are more affected. The most common primary malignant lesion is adenocarcinoma. Most of the clinicians misdiagnosed the metastatic jaw lesion on initial presentation. Factors determining the survival of patients with metastatic jaw lesions could not be ascertained.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12070-024-05120-w.

Key Points

• Metastasis of malignant lesions to the jaw bone is rare.

• Adenocarcinoma is the most common tumor with a tendency to spread to the jaw bones.

• Breast, Lung, and Prostate are the most frequent primary sites of a malignant lesion that metastasizes to the jaws.

Supplementary Information

The online version contains supplementary material available at 10.1007/s12070-024-05120-w.

Introduction

The jaws are affected secondarily by malignant lesions either by a direct extension of a disease from the oral cavity and surrounding structures or by metastasis from a distant site [1]. Metastatic lesions of jaws are very rare and constitute about 1% of all the malignancies occurring in the jaw [1, 2]. Often the primary lesion is diagnosed and treated before the patient is diagnosed with a metastatic jaw lesion [2], However, in some cases, the jaw metastasis may be the initial finding that ultimately leads to the detection of a hidden distant malignant lesion [2].

Metastasis of a cancerous lesion refers to a process by which cancer cells move from their primary site of tumorigenesis and spread to a different part of the body [3]. It results from the complex interplay between the cancerous cells’ molecular properties (e.g. ability to produce the enzymes that digest the intracellular matrix, capability of growth in unfavorable conditions, and capacity to evade the body’s immune system) and the tumor microenvironment [4]. Moreover, organ-specific metastasis is facilitated by multiple factors including tumor-intrinsic factors, organ-specific niches, and the interaction between tumor cells and the host microenvironment [5].

Organotropism differs between various cancer types and subtypes, some prefer metastasizing to the bones (e.g. prostate cancer), while others can metastasize to different sites, including bone, lung, liver, lymph nodes, and brain (e.g. breast cancer, and renal cancer) [3, 6]. In the case of metastasis to the jaws, the mandible is more affected than the maxilla, with the posterior region of the mandible, commonly affected [2, 7]. A previous systemic review of metastatic jaw lesions depicted that males and females were equally affected, and the mean age of patients was 45 years [7]. The primary sites in women are the breasts, reproductive organs, thyroid gland, and kidneys, whereas in men it is in the lungs, prostate, kidneys, bones, large intestine, and suprarenal glands [7, 8].

Since the majority of publications on metastatic lesions to the jaws are case reports and case series a clear pattern of metastasis cannot be established, hence this systematic review aimed to summarize published information regarding metastases to the jaws. The specific objectives were to (1) investigate on common site of primary lesions by age and sex (2) determine the common site of the jaws affected (3) determine factors influencing the survival of patients diagnosed with metastasis to the jaws.

Materials and methods

Data Sources and Search Strategies

A systematic review of the literature was done using PubMed, Scopus, Web of Science, African Journals Online, and Google Scholar electronic databases to identify case reports of patients with metastatic jaw lesions from the years 1950 to 2022. Search words used included “metastatic”, “metastasis to”, and “metastasizing” with a combination of words like “carcinoma”, “jaws”, “mandible”, “maxilla”, “orofacial” and “head and neck”. Other words used were “numb chin syndrome”, “metastatic breast cancer”, “metastatic thyroid cancer”, “metastatic lung cancer”, and “metastatic prostate cancer”. A manual search of references from the obtained literature was also carried out.

Study Selection

The screening of eligible publications was carried out independently by two raters. First, the titles and abstracts of all citations were reviewed. Next, the full texts of potentially relevant citations were reviewed. Discrepancies were resolved by consensus. Cases were only included if (1) the site of primary tumor mentioned; (2) the primary tumor was proved with histologic confirmation and possible radiographic supportive evidence; (3) mandibular and/or maxillary metastasis with histologic confirmation and possible radiological evidence; (4) histologic correlation of the metastatic jaws lesion with a primary lesion; and, (5) in case of anatomical proximity between the primary and metastatic lesion, there should be no tumor tissue between the two foci. Reports were excluded that had no clinical, radiographic, or histologic evidence to confirm the diagnosis of the primary and metastatic lesion.

Data Extraction

Data were extracted by two reviewers and crosschecked by the third. Data from articles published in languages other than English were excluded. The information that was extracted from the selected articles included the authors’ name, the year of publication, the country from where the case was reported, the age and sex of the patient, primary diagnosis, location of the primary lesion, duration between diagnosis of the primary lesion to the diagnosis of metastasis, the jaw bone affected and site of the jaw affected. Other data extracted included previous treatment for primary lesions, treatment for metastatic lesions, and survival time after diagnosing the metastasis.

Data Synthesis and Analysis

Data were summarized using descriptive statistics, with means, standard deviations, medians, and interquartile range (IQR) for continuous variables and frequencies and percentages for dichotomous variables. The countries were divided according to the continents. The age of the patients was grouped into pediatrics (< 18 years), young adults (18–39 years), middle-aged adults (40–59 years), and elderly (60 + years). The primary tissues to be affected were grouped into various appropriate systems except for the breast which was left as a separate entity. The time between primary diagnosis and metastasis was dichotomized into early metastasis (< 5 years) and late metastasis (≥ 5 years). The position of the lesion within jaw bones was grouped as anterior jaw lesions (from the midline to the region of the second premolar for adults, and midline to the region of deciduous canine in children) and posterior jaw lesions (from the region of 1st permanent or deciduous molar to the most distal aspect of the jaw bone). The follow-up period was considered from the time of diagnosing metastatic lesion to the point of outcome during publication of the case.

Univariate analysis was carried out to assess the association between dependent and independent factors. The probability level of α < 0.05 was selected for statistical significance. The strength of the association between various dependent and independent variables was assessed by multivariate logistic regression. The Kaplan-Meier (KM) method was used for survival analysis and KM plots were generated.

Results

Publication Characteristics

The initial search yielded 7492 articles, and 5174 publications were left after removing duplicates. Of these, 678 case reports were identified as potentially relevant and reviewed for full publication. However, after excluding some literature based on exclusion criteria, 450 articles were subsequently reviewed, with a total of 594 documented cases whose description is provided separately [Fig. 1].

Fig. 1.

PRISMA flow chart showing search strategies and screening

The documented cases of metastatic jaw lesions were from 56 different countries. The majority of the cases were reported from the United States of America (N = 147, 24.7%), followed by India (N = 83, 14.0%), and England (N = 40, 6.7%). Others were from Japan (N = 38, 6.4%), and Brazil (N = 24, 4.0%). Overall, the continents of Asia (N = 207, 34.8%), followed by Europe (N = 182, 30.6%), and North America (N = 152, 25.6%) had the majority of reported cases [Fig. 2]. The number of publications of case reports on metastatic jaw lesions increased from 30 cases (in years 1950–1959) to 313 cases (in years 2010–2022). Only 30.5% (N = 181) of the cases were reported before the year 2000.

Fig. 2.

Distribution of reported cases of metastatic jaw tumors in English literature by countries

Age and Sex

The age range of the patients with metastatic jaw lesions ranged from 10 months to 94 years. The mean age of the patients was 54.31 (SD = 19.49) years. The median age was 58 (IQR = 47–68) years. There were slightly more females (N = 299, 50.3%) with a male-to-female ratio of 1:1.01. The mean age for females was 52.00 (SD = 18.22) years and that of males was 56.64 (SD = 20.47) years, and the difference in mean age was statistically significant (p = 0.004). The elderly were the most affected (N = 277, 46.6%), whereas the young adults were the least affected (N = 46, 7.7%).

Primary Lesion

Seventy histological types of malignant lesions were reported to have metastasized to the jaw bones. The most common diagnoses were adenocarcinoma (N = 230, 38.7%), follicular carcinoma (N = 50, 8.4%), hepatocellular carcinoma (N = 46, 7.7%), and squamous cell carcinoma (N = 30, 5.1%). The most common sites of primary lesions with a frequency of more than 40 cases were the breast (N = 107, 18.0%), lungs (N = 84, 14.1%), thyroid (N = 68, 11.4%), liver (N = 47, 7.9%), kidney (N = 43, 7.2%) and prostates (N = 41, 6.9%).

The most common site of primary lesion metastasizing to the jaws in females were the breast (N = 99, 33.1%), thyroid (N = 52, 17.4%), and lungs (N = 27, 9.0%). In males, the frequent sites of the primary lesion were the lung (N = 57, 19.3%) followed by the prostate (N = 41, 13.9%), liver (N = 36, 12.2%), and kidney (N = 28, 9.5%).

The most frequent site of primary lesions metastasizing to the jaws in pediatric patients were the adrenal gland (N = 18, 35.3%) and the eye/orbit (N = 9, 17.6%). In young adults, breast (N = 11, 23.9%) and thyroid (N = 5, 10.9%) were common, whereas in the middle-aged it was the breast (N = 61,12.2%) and lungs (N = 39, 17.7%). The frequent sites of the primary lesion in the elderly were the lungs (N = 41, 14.8%), prostate (N = 37, 13.4%), and breast (N = 35, 12.6%).

Based on the body systems, the genitourinary and the digestive systems were the most affected [Fig. 3]. The primary lesion was diagnosed before metastasis in 368 (61.9%) of cases, while in 226 (38.1%) cases the metastatic jaw lesion was diagnosed before the primary lesion was apparent. In 312 (84.8%) treatment of the primary lesion was done prior to the discovery of metastatic lesion.

Fig. 3.

Distribution of cases according to the system of the primary tumor site

Metastasis

Of the 368 cases of primary lesions diagnosed before metastasis, only 347 (94.3%) had data regarding the interval between diagnosis of the primary lesion to that of the metastatic jaw lesion. This duration ranged between 1 week to almost 31 years after the initial diagnosis, with a median time of 24 months.

The most frequent clinical symptom of the patients with metastatic jaw lesions was jaw swelling (N = 460, 77.4%). Other common symptoms were pain around the jaw region (N = 250, 42.1%), paresthesia of the facial region (N = 117, 29.8%), and trismus (N = 72, 12.1%). Few patients (N = 6, 1%) complained of other symptoms like an unhealed wound, an ulcer, or a change in bite. In 3 patients, the metastasis was an incidental finding.

In the majority (N = 532, 89.5%) of cases the mandible was affected, whereas the maxilla was affected in 61 (10.3%) of the cases, and in one case, both the mandible and maxilla were affected. The metastasis to the mandible was 8.7 more than to the maxilla.

Though in 25 (4.2%) cases, the location of the lesion was not documented, generally, metastasis to the posterior portion of the jaws was 6 times more than to the anterior portion (487 cases to the posterior region versus 82 cases to the anterior portion).

Upon comparing metastasis to only the anterior segment of the jaws, metastasis in the anterior segment of the maxilla occurred more than in the anterior mandibular segment (38.6% and 11.7% respectively). On the other hand, when comparing only the posterior segments of the jaws, it was noted that metastasis in the posterior parts of the mandible occurred more than in the maxillary posterior region (88.3% and 61.4% respectively). This difference was statistically significant (p = < 0.001).

In 241 (40.6%) cases the patient had been given various diagnoses by their primary attending dental professional. The groups of diagnoses included inflammatory disease of the jaw (N = 98, 40.7%), malignant jaw lesion (N = 89, 36.9%), benign jaw lesion (N = 45, 18.7%), and neurogenic condition (N = 9, 3.7%).

A majority (N = 425, 71.5%) of cases with metastatic jaw lesions received treatment for the secondary lesion, however, 94 (15.8%) did not receive any treatment, and in 75 (12.6%) cases it was not documented whether or not the patient received any treatment.

Follow-Up and Outcome

The follow-up period from the point diagnosis of metastatic lesion to when the case was published was documented in 428 (72.1%) cases only. The median follow-up period was 0.54 years (IQR = 0.25–1.33). At the time of publication, 478 (80.5%) cases had their outcome documented. Most (N = 312, 65.3%) had succumbed to the disease [Fig. 4]. In the first year since diagnosis of metastatic jaw lesion, 58.8% of the patient had succumbed to their disease.

Fig. 4.

Percentage distribution of the outcome of the cases at the time of publication

A log-rank test was run to determine if there were differences in the survival distribution of patients with jaw metastasis by various factors including sex and age group of patients, the jaw affected, previous treatment for primary lesion, and treatment of metastatic lesion. The survival distributions for the various factors were statistically insignificant (p ≥ 0.05). The Kaplan-Meier plots are shown in Fig. 5.

Fig. 5.

Kaplan-Meier Plots of survival time of patients with metastatic jaw lesions according to various factors. a) KM plot stratified by sex. b) KM plot stratified by age group.c) KM plot stratified by jaw affected d) KM plot stratified by treatment of primary lesion.e) KM plot stratified by treatment of metastatic lesion

Metastatic Lesions by Sex and Age Groups

The most common site of primary lesions for males was the digestive system followed by the genitourinary system and respiratory system. In contrast, for females, it was the breast, followed by the endocrine system and the genitourinary system. The association between sex and the origin of the primary lesion was statistically significant (p < 0.001) [Table 1].

Table 1.

Distribution of cases of metastatic jaw lesions by sex and age group in relation to the system of origin of the primary lesion

System affected by Primary lesion	Sex		Age group
	Male (N = 295)	Female (N = 299)	Pediatric (N = 51)	Young adults (N = 46)	Middle aged (N = 220)	Elderly (N = 277)
Breasts (N = 109)	8 (2.7%)	99 (33.1%)	-	11 (23.9%)	61 (27.7%)	35 (12.6%)
Endocrine system (N = 91)	32 (10.8%)	59 (19.7%)	18 (35.3%)	7 (15.2%)	33 (15.0%)	33 (11.9%)
Digestive system (N = 122)	90 (30.5%)	32 (10.7%)	1 (2.0%)	6 (13.0%)	37 (16.8%)	78 (28.2%)
Genitourinary system (N = 130)	82 (27.8%)	48 (16.1%)	6 (11.8%)	7 (15.2%)	35 (15.9%)	82 (29.6%)
Nervous system (N = 21)	10 (3.4%)	11 (3.7%)	19 (37.3%)	1 (2.2%)	-	1 (0.4%)
Respiratory system (N = 86)	59 (20.0%)	27 (9.0%)	-	4 (8.4%)	40 (18.2%)	42 (15.2%)
Musculoskeletal system (N = 24)	9 (3.1%)	15 (5.0%)	7 (13.7%)	9 (19.6%)	7 (3.2%)	1 (0.4%)
Cardiovascular system (N = 2)	1 (0.3%)	1 (0.3%)	-	-	-	2 (0.7%)
Lymphatic system (N = 3)	2 (0.7%)	1 (0.3%)	-	-	2 (0.9%)	1 (0.4%)
Integumentary system (N = 8)	2 (0.7%)	6 (2.0%)	-	1 (12.5%)	5 (2.3%)	2 (0.7%)

For pediatric patients, the nervous system and endocrine system were the predominant sources of primary lesions metastasizing to the jaws. On the other hand, for young adults, it was the breasts followed by the musculoskeletal system. The lesions from the breasts and respiratory system were frequent sites of primary lesions metastasizing to the jaws in middle-aged patients, and in the elderly, it was the genitourinary system followed by the digestive system. The relation between age groups and the origin of the primary lesion was statistically significant (p < 0.001) [Table 1].

Upon performing multivariate analysis, for the breast lesions, females were about 17 times more likely to develop jaw metastasis compared to males, and the chances of breast lesions metastasizing to the jaws were 2 folds higher in middle-aged adults compared to the elderly. The chances of jaw metastasis from the endocrine lesion were 213% higher in females than in males, and pediatric patients had 4 times higher odds of having jaw metastasis from endocrine lesions compared to the elderly [Table 2].

Table 2.

Adjusted odds ratio to ascertain the association of sex and age groups of patients with the system of origin of primary lesion metastasizing to the jaws

Age group and sex of the patients	Adjusted Odd Ratio AOR (95%CI, p-value)
	Breast	Endocrine system	Digestive system	Genitourinary system	Respiratory system
Age Groups
Pediatric	0 (0, 0.997)	4.11 (2.06–8.19, < 0.001)	1	1	0 (0, 0.997)
Young adults	1.25 (0.54–2.71, 0.651)	1.05 (0.43–2.59, 0.910)	11.63 (1.32-102.57, 0.027)	1.63 (0.5–5.35, 0.416)	0.74 (0.25–2.22, 0.588)
Middle-aged	2.01(1.25–3.44, 0.004)	1.15 (1.25–3.44, 0.605)	12.81 (1.70-96.52, 0.013)	1.56 (0.61–3.97, 0.348)	1.48 (0.91–2.43, 0.111)
Elderly	1	1	20.75 (2.80-153.85, 0.003)	3.16 (1.29–7.74, 0.012)	1
Sex
Male	1	1	3.55 (2.25–5.59, < 0.001)	1.83 (1.21–2.76, 0.004)	2.74 (1.66–4.54, < 0.001)
Female	16.82 (7.94–35.63, < 0.001)	2.13 (1.31–3.46, 0.002)	1	1	1

Digestive system lesions were 355% more likely to metastasize to the jaws in males compared to females, and the odds of digestive system lesions metastasizing to the jaws increased with age. The chances of jaw metastasis from a genitourinary system lesion were 1.8 folds higher in males compared to females and 3.16 times higher in elderly patients compared to pediatric patients. While the age group had no significant association with jaw metastasis from respiratory systems, the odds of jaw metastasis from a lesion originating from respiratory systems were almost 3 times higher in males compared to females [Table 2].

The Jaw Affected According to the Sex, Age Groups, and System of Primary Lesion

Though there was no statistically significant association between metastasis to either the mandible or maxilla with the primary lesion’s system of origin and age groups, the sex of the patient, on the other hand, had a statistically significant association (p = 0.0001). The odds of mandibular metastasis in females were 4 folds higher than those of males [OR 4.27, 95%CI 2.26,8.08, p < 0.001]. On the contrary, males were almost 4 times more likely to develop maxillary metastasis compared to females [OR 3.97, 95%CI 2.13,7.35, p < 0.001].

Discussion

Metastasis refers to the development of a secondary lesion in a site away from the original location of the primary tumor in the body [3, 9]. It is a rare event because for cancerous cells to become apparent in different organs it must overcome multiple factors [5, 9]. Furthermore, metastasis to the jaws is even rarer, hence majority of publications on metastatic lesions to the jaws are either case reports or case series. Taking this into consideration the aim of this study was to collect and analyze published data regarding metastatic lesions to the jaws.

In this systematic review of cases, a majority of cases were from the USA, India, and England. Such findings may be attributed to the literature search strategy utilized, i.e. only data of articles published in languages were included in the study. It is worth noting that there were very few documented cases of jaw metastasis in the African population. Such findings are not surprising though since it has been reported that only 1.5% of scientific literature is from the African continent [10]. Considering that the African population accounts for about 16.5% of the world´s population [11], it may be presumed that the cases of metastatic jaw tumors are vast, however, due to a lower tendency of publishing, they go unnoticed.

The findings of this analysis pointed out a significant increase in the number of publications after the year 2000, such findings may be attributed to the massive technological advances. With advances in medicine, the detection of metastatic lesions in the jaw is more accurate in the current era. Moreover, with improved internet communication, the number of online journals and databases has increased [12], as such the limitation of paper space within printed journals becomes less of a concern, and thus many deserving articles that were previously rejected on a space basis can be accommodated, hence published.

The data from the current study demonstrate an almost equal number of females and males, similar to the findings of Hirshberg et al. [13]. On the contrary, previous studies have indicated male predominance of the disease at a proportion that ranges from 1.08 to 1.35 [7, 8, 14–16]. The difference noted between studies may be attributed to the methodology of the study including the search strategies. Despite this, considering the small difference in the proportion of males and females affected, it may be generalized that both genders are equally affected, and the sex of the patient may not be a direct factor in determining the metastasis of malignant lesions to the jaws.

In this survey, the mean age of patients at diagnosis of metastatic lesion was 54.4 years. These findings were similar to reports of other surveys conducted in the past [7, 8, 14, 16]. The findings of all systemic reviews of cases point out that on average females developed metastasis to the jaws 3 to 5 years earlier than the males. Though the development of metastasis is a multifactorial phenomenon, recently it has been demonstrated that various molecular interactions in tumorigenesis and metastasis formation are influenced by sex and differences in sex hormone levels [17]. The endocrine pathways regulated by estrogen, progesterone, or androgen have been identified to control the cancer bone cell cross-talk during the process of bone metastasis formation [17–19]. Taking this into account, among other reasons, it may be a sound explanation for findings that jaw bone metastasis occurs earlier in women than men considering women tend to undergo menopause earlier than males undergoing andropause.

In this study, about seventy different histological types of malignant tumors were reported, and as per the reports of previous studies [7, 13, 14], the most frequent diagnosis was adenocarcinoma. The high incidence of adenocarcinoma metastasizing to the bone can partially be explained by it being a common malignant lesion, thus the probability of finding it metastasizing to the bone increases. However, the role of the biological behavior of the tumor, its degree of aggressiveness, and possible preference toward osseous structures cannot be overlooked [15].

Comparable to the reports of other authors [7, 13, 20, 21], in this systemic analysis of cases, the most frequent sites of primary lesions, in general, were the breast, lungs, thyroid, prostate, kidney, and liver. The variation in the occurrence of these malignant lesions according to the sex of the patient defined the differences in incidence between males and females.

The findings of the current analysis depict that the most frequent site of primary lesions metastasizing to the jaws in children was the adrenal gland. In contrast, in adults it was the breast and lungs, and in the elderly was the lungs, prostate, and breast. Similarly, Hirshberg et al. [13] found that the primary site differed with age. In the first decade, the adrenals were the most common primary site and in the older groups, it was the breast for women and for men, it was prostates and lungs. Ryan and colleagues [22] inferred that for patients with > 25 years the primary site for bone metastasis is lung, breast, and prostate cancer; for those patients < 20 years, it is the endocrine cancers and soft tissue sarcomas.

From the current study, it is apparent that metastasis to the jaw bone can be detected before the primary lesion considering the finding that in almost 40% of the cases reported in the literature, the jaw lesion was diagnosed first. We also found that in almost 40% of the cases, the primary clinician misdiagnosed the metastatic lesion for other conditions like inflammatory jaw disease. It often may be challenging for clinicians to have a differential diagnosis of a metastatic lesion to the jaw bone [23]. The difficulty is due to their rarity, in addition to the signs and symptoms (such as toothache, swelling, trismus, neurological disturbances, and joint pain) that overlap with other disease conditions of the jaw [16]. However, with proper history taking and careful examination of the patient, the chances of diagnosing metastatic jaw lesions increase. Symptoms like anesthesia or paresthesia over the chin, lower lip, and submental area (numb chin syndrome) should always raise the possibility of a metastatic lesion in the mandible [7].

Though there was no statistically significant association between metastasis to either the mandible or maxilla with the primary lesion’s system of origin and age groups, the sex of the patient, on the other hand, had a statistically significant association. Females were 4.3 times more likely to present with mandibular metastasis compared to males, whereas, males were almost 4 times more likely to develop maxillary metastasis compared to females. Though the exact reason for such a difference cannot be ascertained, it can be speculated that the biological behavior of the primary tumor and the molecular interaction of the tumor cells to the bone may have some role to play, in addition to the role of hormones and genetics of an individual [24]. this topic may be worth investigating.

The probability of survival at one year was 41.2%, results which were slightly higher than the findings of Lopes et al. [16] who reported a probability of 31.7% in patients with metastasis to the oral cavity. There was no difference in the probability of survival when comparing the patients by sex and age groups, the jaw affected, previous treatment for the primary lesion, and treatment of the metastatic lesion. Though evidence is scarce in the literature regarding the factors affecting life expectancy in patients with skeletal metastasis, comparable to our findings, Zacharia and colleagues [24] also noted no significant association between gender, mode of treatment, and life expectancy. However, to the contrary, they reported a significant association between life expectancy and the type of detection of bone secondaries, site of primary, bone metastasis with unknown primary, and mode of presentation in patients with skeletal metastasis. The differences noted between the findings of this systemic analysis and the results of Zacharia et al. [24] may be due to different types of study. Whereas this survey was specifically for jaw bone metastasis, the other study was a prospective cohort study.

Our study has several limitations, including the language restriction we applied, as such publications in other languages (Spanish, Chinese, German, etc.) were not used. The quality of the case reports, and the lack of complete information in some of the case series and case reports were a setback. The influence of other confounding factors and heterogeneity inherent in the included case studies was another limitation. Despite these limitations, to date, this is the most comprehensive study on this topic. This systemic analysis augments the existing literature through the evaluation of cases of jaw bone metastasis, and the impact on survival by age, sex, the jaw affected, previous treatment for primary lesion, and treatment of metastatic lesion. This study casts light on the metastatic jaw lesions, hence can assist clinicians in developing a differential diagnosis for jaw lesions and provides estimated survival time.

Conclusion

Metastasis of malignant lesions to the jaw bone is a rare event and has a poor prognosis, with a one-year probability of survival being 41.2%. Females and the elderly are more affected. The most common primary malignant lesion is adenocarcinoma. The frequent primary sites in females are the breast and thyroid while in males it is the lungs and the prostate. Jaw swelling, pain, and paresthesia are among the frequent symptoms. Most of the clinicians misdiagnosed the metastatic jaw lesion on initial presentation. The survival of patients with metastatic jaw lesions does not depend on the demographics of the patient, the primary site, and the treatment of the primary lesion. We recommend that considering the fatality of the condition, it is of utmost importance to detect the disease early. Metastatic jaw tumors should be considered in the differential diagnosis of jaw lesions, especially if the patient has a positive history of malignancy, and has numb chin syndrome.

Electronic Supplementary Material

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Author contributions

K.S. Sohal: Conceptualization, Literature search, Analysis and interpretation, Writing an original draft, Editing. U.Okechi: Literature search, Methodology, Supervision; Reviewing and Editing. R.Grillo Literature search, Methodology, Supervision; Reviewing and Editing. R. Ruparellia: Conceptualization, Supervision, Reviewing and Editing. A.S.Sohal: Analysis and interpretation, Editing Investigation.

Funding

This research did not receive any specific funding.

Declarations

Ethical committee approval

Not Applicable.

Informed consent

Not Applicable.

Conflict of Interest

The authors declare that they have no conflicts of interest about this article.