Abstract
Metastatic lesions to the jaws are rare. The oral sites to which metastasis most commonly occur are the jaws, the gingiva, and the tongue. Lower jaw is a more frequent site of metastasis compared to the upper jaw with posterior areas (ramus, body) that are more prone to the deposition of cancerous cells due to presence of hematopoietic bone marrow, subdivision of local blood vessels and reduced velocity of blood flow. In fact, the formation of secondary foci of tumor colonization occurs by hematogenous dissemination of tumor emboli, that accumulate in regions with larger amounts of bone marrow and low circulatory velocity. In females, commonly seen metastatic lesions arise from primary neoplasms in breasts, colon, genitals and thyroid glands, whereas in males arise from lungs, prostate and colon region. Patients with metastatic jaw disease may be asymptomatic or may show various clinical signs and symptoms that include pain, swelling, paresthesia, foul smell, tooth mobility, exophytic growths of the soft tissues, reduced mouth opening and, infrequently, pathological fractures. In particular, metastasis in breast cancer is commonly seen in the lungs, liver, bones, pleura, brain, and kidneys, whereas breast cancer metastasis to the oral cavity is not common and is seen in only around 1% of the cases. Breast cancer can also be latent where the metastases appear years after treatment of the primary tumor. The presence of metastasis is highly important in determining the patient’s prognosis and mode of treatment. The aim of the present article is to present and discuss the diagnosis of a breast cancer metastasis in the mandibular angle.
Keywords: Breast cancer, Metastasis, Mandible, Biopsy, Diagnosis
Introduction
Metastatic lesions to the jaws are rare. The oral sites to which metastasis most commonly occur are the jaws, the gingiva, and the tongue. Lower jaw is a more frequent site of metastasis compared to the upper jaw with posterior areas (ramus, body) that are more prone to the deposition of cancerous cells due to presence of hematopoietic bone marrow, subdivision of local blood vessels and reduced velocity of blood flow [1–12].
In fact, the formation of secondary foci of tumor colonization occurs by hematogenous dissemination of tumor emboli, that accumulate in regions with larger amounts of bone marrow and low circulatory velocity [1–5].
In females, commonly seen metastatic lesions arise from primary neoplasms in breasts, colon, genitals and thyroid glands, whereas in males arise from lungs, prostate and colon region.
Patients with metastatic jaw disease may be asymptomatic or may show various clinical signs and symptoms that include pain, swelling, paresthesia, foul smell, tooth mobility, exophytic growths of the soft tissues, reduced mouth opening and, infrequently, pathological fractures [1–7].
In particular, metastasis in breast cancer is commonly seen in the lungs, liver, bones, pleura, brain, and kidneys, whereas breast cancer metastasis to the oral cavity is not common and is seen in only around 1% of the cases. Breast cancer can also be latent where the metastases appear years after treatment of the primary tumor. The presence of metastasis is highly important in determining the patient’s prognosis and mode of treatment [1, 3, 5, 8, 9, 12].
The aim of the present article is to present and discuss the diagnosis of a breast cancer metastasis in the mandibular angle.
Case Report
A 47-year-old woman was referred to the Division of Dentistry for a dental assessment in anticipation of a possible antiresorptive treatment. The woman was affected by a metastatic breast ductal infiltrative G2 adenocarcinoma. The patient had undergone a radical mastectomy 9 years before, and in the last years the patient had developed numerous metastasis to the skin, the sacrum, the left iliac bone, the C6, C7, L4 and L5 vertebrae, and the skull. A IV stage was diagnosed and the patient had undergone chemotherapy.
At the dental consultation, the patient did not refer any sign or symptom in correspondence of the oral cavity.
Clinical examination was unremarkable. No intraoral lesions could be observed.
A CT scan performed in 2021 did not reveal any lesion in correspondence of the jaws or the neck region (Fig. 1).
Fig. 1.
Coronal (a) and axial (b) CT scan, performed in 2021, showing the absence of pathological images in correspondence of the mandible
A panoramic radiograph performed in January 2023 revealed a dishomogeneous mixed radiopaque —radiotransparent are in the left mandibular angle region distally to the inferior left second molar (Fig. 2).
Fig. 2.
Panoramic radiograph, performed in January 2023, revealing a dishomogeneous mixed radiopaque—radiotransparent in the left mandibular angle region distally to the inferior left second molar
Therefore, a new maxillofacial CT scan was prescribed and performed: The CT scan confirmed the presence of an ill-defined radiotransparent osteolytic soft tissue density mass lesion in the left mandibular angle region. Erosion of both the lingual and vestibular cortical bone was found (Fig. 3).
Fig. 3.
Coronal (a) and axial (b,c) CT scan, performed in 2023, confirming the presence of an ill-defined radiotransparent osteolytic soft tissue density mass lesion in the left mandibular angle region. Erosion of both the lingual and vestibular cortical bone was found
An incisional biopsy under local anesthesia was immediately proposed to the patient, that agreed.
Under local anesthesia, an incision in the vestibular mucosal region of the left angle was performed, corticotomy by round bur handpiece was executed and the presence of a whitish lardaceous hard intrabony mass was observed. A biopsy of the mass was performed. The surgical wound was then sutured.
Histopathological examination established the diagnosis of a metastasis from a breast ductal infiltrative G2 adenocarcinoma (ER: 100%; PR: 100%; HER2neu: 0).
Finally, the patient underwent a multidisciplinary oncological assessment, that suggested palliative medications and chemotherapy.
Discussion
Patients with metastatic disease localized in the jaws may be asymptomatic or they may show several clinical signs and symptoms, including pain, paresthesia of the upper lip, extruded teeth, regional lymphadenopathy, maxillary nerve involvement and numb cheek syndrome, cortical expansion of the jawbones, trismus, and exophytic growth. The mandible is affected more frequently than the maxilla, with a predilection for the body and ramus. In fact, these sites are thought to be more vulnerable to the deposition of neoplastic cells because of hematopoietic bone marrow, branching of the local blood vessels and slowing of blood flow [1–9].
Metastases of breast cancers to bones identified to cause osteolytic lesions secrete biological mediators along with interleukin IL-11, IL-8, and IL-6, parathyroid hormone-related protein (PTHrP), that induce osteoclast-mediated bone resorption through activation of the RANK/RANKL/OPG signaling pathway. These mediators up regulate the expression of RANKL and down-regulate the expression of L(OPG) by osteoblasts and other stromal cells, as a consequence of promoting osteoclast differentiation and activation, culminating in bone resorption [1–7].
Breast carcinoma can spread locally as well as cause distant spread through lymphatics and the bloodstream. Breast cancer metastases commonly spread to the lungs, liver, bones, pleura, and kidneys. The carcinoma spreads to the mandible through the bloodstream. In females, the majority of the mandibular metastasis is from the breast. Table 1 resumes the encountered histotypes of metastatic breast cancer to the oral region in the literature. It is important that the dental practitioners remembers that metastasis can even appear in patients after a prolonged disease-free period [1–6].
Table 1.
Histotypes of metastatic breast cancer to the oral region
| Histotype | Immunohistochemistry |
|---|---|
| AdenoCarcinoma | CK7 ± ; ER ± ; PR ± |
| Lobular Carcinoma | ER; PR |
| Ductal Carcinoma | CK7; ER; PR |
| Malignant Phylloides tumor | Vimentin; actin; CD34 |
| Angiosarcoma | CD34 |
The radiographic appearance of metastatic disease in the jaws is variable, ranging from well circumscribed to poorly circumscribed radiolucent lesions; the latter are also known as ‘‘moth eaten’’ lesions. Since metastatic neoplasms from the breast and prostate stimulate bone formation, this metastasis may also appear as mixed lesions.
The prognosis for patients with metastatic lesions of the oral cavity is usually poor. The management of metastatic maxillary lesions from the breast carcinoma is primarily palliative and may include pain relief, radiotherapy, chemotherapy, hormone therapy and, rarely, surgical intervention [1–9].
In conclusion, metastatic bone metastasis should be considered in the differential diagnosis of osteolytic lesions of the jaws. A particular attention should be paid in patients with past medical history including cancer. This case emphasizes the importance of a complete diagnostic work-up including a detailed medical history as well as careful clinical, radiographic and histopathological examination.
Declarations
Conflict of interest
The authors have not disclosed any conflicts of interest.
Human and Animals Rights
No experimental studies performed.
Informed Consent
Informed consent was obtained by the patient.
Footnotes
Publisher's Note
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