Mandibular metastasis of invasive ductal carcinoma of the breast: a case report

Abstract

Background

Metastasis of breast carcinoma to the oral cavity is an uncommon event, and mandibular involvement is even rarer. This case is notable owing to the delayed occurrence of mandibular metastasis 6 years after the primary diagnosis, highlighting its aggressive behavior, which resulted in a pathological mandibular fracture. Reporting such rare presentations can aid clinicians in identifying atypical metastatic patterns in breast cancer survivors.

Case presentation

A 45 year-old Persian female with a history of invasive ductal breast carcinoma, diagnosed initially and treated 6 years earlier, presented with facial swelling and pain in the left lower jaw. She had been receiving bisphosphonate therapy for bone metastases. Clinical and radiographic evaluations revealed a radiolucent mandibular lesion with cortical bone perforation. Histopathological and immunohistochemical analyses confirmed metastasis from the primary breast cancer. Despite subsequent radiotherapy and chemotherapy, the lesion progressed, resulting in a pathological mandibular fracture and further metastases to the lungs and liver.

Conclusion

This case underscores the importance of considering metastatic disease in diagnosing oral lesions in patients with a history of malignancy. Early recognition of atypical presentations such as mandibular metastasis may facilitate timely intervention, although prognosis remains poor in such advanced stages.

Background

Globally, breast cancer constitutes a major public health concern, being one of the most prevalent malignancies affecting women. In Western societies, it is the second leading cause of cancer-related mortality and ranks sixth among the primary causes of death in the female population [1, 2]. A wide metastatic distribution is observed in breast cancer, with preferential involvement of the lungs, lymph nodes, bones, pleura, and liver [3, 4]. Breast carcinoma ranks among the most frequent primary malignancies associated with metastatic involvement of the head and neck region [5].

Metastasis represents an advanced and often critical phase of cancer progression, characterized by the dissemination of malignant cells from the primary tumor to distant organs or tissues via lymphatic channels or the hematogenous route [6, 7]. Diagnosing metastatic lesions in the oral cavity is challenging for clinicians and pathologists [8]. Clinicians must include the possibility of metastatic lesions in their differential diagnosis, while pathologists must identify the tumor’s origin. Diagnosing mandibular metastasis remains particularly challenging owing to its clinical rarity, insidious onset, and nonspecific symptomatology, which collectively contribute to frequent delays in definitive diagnosis. Despite the diagnostic challenges, early identification of such lesions is paramount, as they may represent the initial clinical manifestation of an occult distant primary malignancy or indicate metastatic involvement from a previously diagnosed neoplasm [9, 10].

Metastasis of malignant tumors in the oral cavity is rare, representing about 1% of all oral tumors [11]. A large-scale retrospective analysis of 2039 patients with oral malignant tumors conducted over 32 years at Seoul National University Dental Hospital identified only 21 cases (1.03%) of metastatic carcinoma to the oral region, providing robust evidence for the low prevalence of this condition [12]. Furthermore, among the various primary origins of malignancy, the most commonly implicated are lung (17.3%), breast (12.6%), kidney (12.5%), and liver (8.9%) [11]. Metastatic breast cancer accounts for approximately 0.13% of all malignant tumors in the oral cavity [11]. Metastatic involvement of the oral cavity generally manifests in the late phases of malignancy progression and is often accompanied by substantial functional and symptomatic morbidity [13]. This condition frequently reflects advanced-stage malignancy and is associated with an unfavorable prognosis, with a 5-year survival rate reported to be below 5%.

Metastatic tumors in the oral cavity are uncommon, representing less than 1% of all malignancies documented in this region [13]. Metastatic involvement can affect the oral soft tissues, jawbones, or a combination of both regions [14]. Oral metastatic lesions are more commonly found in the mandible than the maxilla, particularly in the posterior regions [8, 13, 15]. The presence of hematopoietic bone marrow, multiple blood vessel branch points, and slow blood flow are believed to contribute to this site preference [16]. Metastatic lesions to the oral cavity often present with a range of clinical manifestations, including localized inflammation, pain, and swelling. Common symptoms may encompass paresthesia, loosening or extrusion of teeth, halitosis, and regional lymphadenopathy. Involvement of the mandibular nerve may result in numb chin syndrome, while cortical expansion of the jawbones, mucosal ulceration, trismus, and exophytic masses are also frequently observed. In rare instances, these lesions may lead to pathological fractures of the affected bone [17, 18].

Metastatic lesions within the oral cavity typically lack pathognomonic radiographic characteristics, and imaging findings are often inconclusive. As a result, histopathological confirmation remains essential for definitive diagnosis. In the jaw, these lesions may present with a spectrum of radiolucent patterns, ranging from well-demarcated to ill-defined margins, the latter commonly described as having a “moth-eaten” appearance [19]. Metastatic lesions originating from the breast and prostate may induce osteoblastic activity, developing mixed lytic-sclerotic bone lesions. Occasionally, owing to the clinical and radiographic similarities, these lesions may be misinterpreted as inflammatory or infectious pathologies affecting the jaws and surrounding structures [20].

This case is reported owing to its rarity and clinical significance. The occurrence of mandibular metastasis from invasive ductal carcinoma of the breast is highly uncommon, especially when it presents several years after the primary cancer diagnosis. The delayed onset, insidious progression, and diagnostic complexity make this case particularly noteworthy. By highlighting the diagnostic challenges and unusual clinical course, this report contributes to the limited body of literature. It underscores the importance of considering metastatic disease in patients presenting with atypical oral symptoms and a history of breast cancer.

Case presentation

A Persian female patient, 45 years old, was referred to the Oral Medicine Department, Dental Faculty, Tehran University of Medical Sciences, with a history of breast cancer 6 years ago and current bisphosphonate (zoledronic acid) use. The patient had been receiving intravenous zoledronic acid at a dose of 4 mg every 3 weeks for 18 months. She presented with an intra-mandibular radiolucent lesion with cortical perforation, and swelling was noted on the left side of the patient’s face and submandibular region (Fig. 1). Given the radiographic appearance and site of the lesion, several differential diagnoses, such as central giant cell granuloma, odontogenic keratocyst, lymphoma, and primary intraosseous carcinoma, were initially considered. On the basis of clinical and radiological evidence and a medical history of breast carcinoma, with a differential diagnosis of breast cancer metastasis, a cone-beam computed tomography (CBCT) radiograph was obtained. A CBCT study revealed a radiolucent 20 mm × 17 mm × 14 mm mass with poorly defined borders in the posterior edentulous region of the left mandible, causing expansion and perforation of the buccal cortical plate.

Fig. 1.

Clinical view of the patient: a noticeable swelling was observed over the left hemiface, extending into the submandibular area

The cortical border of the inferior alveolar nerve was not visualized (Fig. 2). Based on clinical and radiographic findings, the differential diagnosis included metastatic breast cancer and low-grade malignancy. However, owing to the patient’s oncologic history and the aggressive behavior of the lesion, metastasis was the most likely diagnosis. An incisional biopsy was performed on the lesion, measuring 1.2 cm × 0.5 cm × 0.5 cm with a solid, homogeneous cream surface. Histopathologic examination showed small nests and individual cells with marked nuclear atypia, hyperchromatism, and prominent nucleoli within a highly collagenized stroma. Numerous mitotic figures, including atypical mitosis, were observed.

Fig. 2.

Cone beam computed tomography views of the mandible. (A) Panoramic Cone beam computed tomography showing the lesion in the posterior mandible. (B) 3D reconstruction view illustrating the buccal cortical plate perforation. (C) Axial view indicating the extent and location of cortical bone destruction

Immunohistochemistry tests were conducted, revealing negative results for estrogen receptor (ER), progesterone receptor (PR), S100 protein (S100), and leukocyte common antigen (LCA). At the same time, cytokeratin 7 (CK7) and GATA binding protein 3 (GATA3) were diffusely positive in tumor cells, and human epidermal growth factor receptor 2 (HER-2) immunoreactivity demonstrated weak-to-moderate membranous staining in more than 10% of the neoplastic cells (Fig. 3). The final diagnosis was high-grade carcinoma with histopathological and immunohistochemical findings consistent with metastatic breast cancer. A subsequent referral to an oncology service was arranged to facilitate ongoing evaluation and treatment. The current treatment plan for the case is 17 fragments of head and neck radiotherapy with a total dose of 60 Gray in the form of intensity-modulated radiotherapy (IMRT). After radiotherapy, the lesion grew larger, resulting in a lower jaw fracture. Further examination revealed that the primary tumor had metastasized to the lungs and liver. Unfortunately, her condition remained palliative due to widespread metastases, and she passed away 6 months after the diagnosis of mandibular metastasis.

Fig. 3.

(A) The hematoxylin and eosin staining shows nests and individual epithelial cells with prominent anisonucleosis and numerous mitotic figures, including atypical mitoses (400×). (B) Almost negative immunostaining for progesterone receptor (100×). (C–E) Negative immunostaining for estrogen receptor, S100, and leukocyte common antigen (100×). (F, G) Positive immunostaining for CK7 and GATA3. (H) HER-2 immunoreactivity demonstrated weak-to-moderate membranous staining in more than 10% of the neoplastic cells

Discussion

Breast cancer represents the most prevalent malignancy among women and constitutes the leading cause of cancer-related mortality in females between the ages of 20 and 59 years [21]. Breast cancer constitutes approximately 26% of all newly diagnosed malignancies in females and remains a leading cause of cancer-related mortality, accounting for 15% of cancer deaths among women. Although advances in early detection and therapeutic strategies have led to improved overall prognosis, disease progression to distant metastatic sites occurs in an estimated 20–30% of cases. The most commonly affected organs include the bone, liver, lungs, and brain [22, 23]. In breast cancer, the bone constitutes the predominant site of distant metastasis, with approximately 75% of patients with stage IV disease exhibiting skeletal involvement [24]. The spine, ribs, sternum, femur, and pelvis are common sites for bone metastases in patients with breast cancer [25]. Oral cavity metastases are rare, comprising only 1–3% of all malignant lesions identified within the oral region [13, 26]. The mandible is more frequently involved than the maxilla, with a predilection for regions posterior to the canines, particularly the mandibular body and ramus [9, 10, 27]. Table 1 summarizes documented cases of breast cancer metastasis to the jaw. The jawbone contains abundant hematopoietic tissue, which may serve as a receptive site for circulating tumor cells owing to its rich vascularization. Since metastatic spread typically occurs via the hematogenous route, diminished blood flow within this region might promote the entrapment and implantation of malignant cells [28].

Table 1.

Oral cavity involvement by metastatic breast cancer cases reported in the literature

Author	Year	Sex*, age	Location	Treatment	Follow-up
Spirito et al. [33]	2024	F*, 32	Mandibular, paresthesia/anesthesia in the left mandibular area,	Surgical intervention was not performed, and the patient was referred to an oncologist for further systemic treatment	NA**
Rodrigues et al. [34]	2024	F, 55	Right mandibular ramus region, numbness on her lower lip and chin	Patient was subsequently referred to her oncologist	Patient developed mandibular swelling and facial asymmetry, and died 3 years after diagnosis
Soualem et al. [10]	2024	F, 66	The posterior region of the lower right mandible	Chemotherapy before oral surgery + intravenous zoledronic acid was administered at a dose of 4 mg every 3 weeks for the management of bone metastasis	NA
Boffano et al. [35]	2023	F, 47	Region of the left mandibular angle, distal to the inferior second molar on the left	Palliative medications and chemotherapy	NA
Sadasivan et al. [36]	2022	F, 37	Maxillary gingiva between tooth no. 8 and 9	Wide excision with a 2 mm safe margin + chemotherapy (eribulin)	Satisfactory healing after 3 months but unfortunately died
Vetri et al. [37]	2022	F, 37	Angle of the right mandible	External beam radiotherapy + palliative chemotherapy (adriamycin, cyclophosphamide, and zoledronic acid) + hormone therapy	Under treatment from 2019 to 2022
Chang et al. [38]	2021	F, 56	Right mandibular condyle	Palliative treatment with chemoradiation therapy	At 3-month follow-up, pain in the right temporomandibular joints (TMJ), function and mouth opening improved with ongoing treatment
Magat et al. [19]	2019	F, 40	The bilateral coronoid processes, condyles, and rami of the mandible	NA (referred to her oncologist)	NA
Dodo et al. [39]	2017	F, 55	Left mandibular condyle	Chemotherapy (fluorouracil, epirubicin, and cyclophosphamide)	Died after 36 months
Azadeh et al. [40]	2016	F, 49	The body and ramus of the left mandible bone	Radiation therapy over 2 weeks	NA
Thorawat et al. [27]	2015	F, 45	Body of the right mandible	Wide surgical excision	Died after 3 months
Varghese et al. [18]	2014	F, 40	Angle of the left mandible	NA (referred to her oncologist)	NA
Qiu et al. [41]	2013	F, 47	Right condyle of the mandible	En bloc extirpation of the tumor together with the right condyle and ramus + adjuvant radiotherapy	Alive without any sign or symptom after 12 months
Perez et al. [42]	2012	M, 73	Body and condyle of the left mandible	Surgery of the primary tumor + left mastectomy with axillary dissection + hormonal therapy + chemoradiation therapy	Remained disease-free after 3 years
Kechagias et al. [43]	2011	F, 52	Buccal mucosa located in the molar region of the left side of the mandible	Radio-chemotherapy	No signs of recurrence after 13 months
Khalili et al. [44]	2010	F, 40	Right mandibular second premolar	Change Tam method of chemotherapy	Pulmonary metastasis after 15 months, alive after 20 months (end stage of disease)
Otto et al. [45]	2010	F, 53	Left mandibular body	Radiotherapy	Died after 6 months

^*F, female; M, male

^**NA, not available

Diagnosing metastasis in the oral cavity poses a significant challenge owing to the absence of pathognomonic signs and symptoms [29]. Metastatic tumors involving the oral cavity may exhibit a broad spectrum of clinical manifestations, including but not limited to localized pain, soft tissue swelling, paresthesia, halitosis, gingival irritation, increased dental mobility, exophytic soft tissue masses, trismus, cortical bone perforation, and, albeit infrequently, pathological fractures [30]. In this case, we encountered a rapidly growing solid mass that had perforated the buccal cortical bone of the posterior mandible. In the case of distant metastasis, a median duration of 29.0 months has been observed between the primary diagnosis and the onset of initial metastatic spread, demonstrating a median overall survival of approximately 31.0 months after the onset of metastasis. Accurate examination and microscopic evaluation are crucial for early detection [25, 31]. Oral cavity involvement by metastatic malignancies is linked to a poor prognosis and can be life-threatening. Less than 10% of patients survive for more than 4 years after diagnosis [32]. The primary goals in managing metastatic breast carcinomas in the oral cavity are pain relief and prevention of infections, fractures, or hemorrhage. Nevertheless therapeutic intervention for the oral lesion should be conservative and minimally invasive when the primary tumor recurs or remains untreated. Owing to the delayed diagnosis, advanced nature of the lesion, and severe clinical conditions such as bone perforation, radiotherapy and chemotherapy were administered simultaneously.

Metastatic lesions in the oral region are rare and challenging to diagnose owing to nonspecific signs. Common features include swelling, persistent pain, paresthesia, and unexplained tooth mobility. Gingival metastases often mimic benign lesions, while jaw metastases typically affect the posterior mandible and may cause numb chin syndrome, indicating nerve involvement. Radiographically, these lesions are usually osteolytic but can mimic cysts or osteomyelitis. Recognizing these signs is crucial for early detection. Recent case reports have underscored the diagnostic challenges posed by mandibular metastases originating from breast carcinoma [33, 34]. For instance, a case with a history of treated breast cancer presented with mandibular lesions that were initially misinterpreted owing to their atypical radiographic appearance. The lesions mimicked benign conditions, leading to a delay in accurate diagnosis [34]. Similarly, a case where metastatic involvement of the mandibular angle from breast carcinoma was initially overlooked emphasizes the need for heightened clinical suspicion, especially in patients with a known history of breast cancer [34]. These cases align with our findings, reinforcing the importance of considering metastatic disease in the differential diagnosis of mandibular lesions, particularly when patients present with nonspecific symptoms such as swelling or pain.

Conclusion

Metastatic involvement of the mandible, although rare, must be considered in the differential diagnosis of persistent jaw lesions, particularly in patients with a history of breast carcinoma. Early recognition of clinical red flags, such as mandibular swelling, paresthesia, or unresponsive dental symptoms, should prompt timely imaging and biopsy to avoid diagnostic delay. This case underlines the importance of considering metastatic disease in patients with a history of breast cancer who present with oral symptoms. Early recognition and biopsy are key to appropriate management.

Abbreviations

CBCT

Cone-beam computed tomography

CK7

Cytokeratin 7

ER

Estrogen receptor

GATA3

GATA binding protein 3

HER-2

Human epidermal growth factor receptor 2

IMRT

Intensity modulated radiotherapy

LCA

Leukocyte common antigen

PR

Progesterone receptor

S100

S100 protein

Author contributions

All authors contributed equally to the preparation, writing, and final approval of this manuscript.

Funding

No funding.

Data availability

Data related to this case are available from the corresponding author upon reasonable request, with appropriate ethical and patient consent considerations.

Declarations

Ethics approval and consent to participate

This study was conducted on selected patients with head and neck cancer, with approval granted by the Tehran University of Medical Sciences Ethics Committee and adhered to relevant guidelines and regulations. All methods were performed in accordance with the Declaration of Helsinki [46]. Enrolled patient were informed about the study’s purpose and procedures. After obtaining their written informed consent, as per the ethics committee requirements at the participating institutions, the study commenced.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interests.