Metastatic adenocarcinoma of mandible: in search of the primary

Abstract

We present here a case of a 64-year-old female patient who reported with a complaint of pain in the chin region of 3-month duration. The radiographs revealed an irregular radiolucent lesion in the anterior part of the mandible. An incisional biopsy was carried out and the microscopy showed features of adenocarcinoma. Suspecting a metastatic lesion, the patient was then sent for whole body examination which showed a mass in the lungs. A whole body scan also showed metastasis to other organs such as kidney, gallbladder and vertebrae. This case is unusual in that the patient complained only of a vague jaw pain with no other systemic symptoms even in the presence of widespread disease.

Background

Metastasis to the oral cavity is comparatively less common and comprises about only 1% of all oral and maxillofacial malignancies.¹ The majority of metastatic cases reported in the literature have primary tumours located in the lung, breast, kidney and colon. They are usually intraosseous (90%) with soft tissue localisations being rare.² The diagnosis of metastatic malignancy requires a thorough examination of the biopsy sample and immunohistochemical analysis along with whole body examination. In this case report, we wish to highlight the fact that the diagnosis of a metastatic lesion in the oral region is often challenging to the pathologist, especially if it is the first symptom shown by the patient.

Case presentation

A 64-year-old female patient reported with a complaint of pain in the chin region for the past 3 months. The patient initially consulted a local dentist for pain in the lower front teeth which was decayed, subsequent to which she underwent extraction of 41, 42 and 43. However, the pain did not subside and further, she developed a swelling in the region which progressively increased in the next 3 months. She was then referred to the oral and maxillofacial centre at our hospital. The general examination did not reveal any abnormalities and she was apparently healthy. On examination, she had slight facial asymmetry due to a diffuse swelling below the lower lip on the right side which was extending below the chin (figure 1). She also had paraesthesia of lower lip and chin. On palpation, there was a local rise in temperature and tenderness in the area. There was no palpable lymph node in the neck region. Intraoral examination showed a diffuse swelling obliterating the labial vestibule from 41 to 44 region. The extraction sockets had healed well and there was no change in the superficial oral mucosa.

Figure 1.

Diffuse swelling below the lower lip on the right side which was extending below the chin.

Investigations

The patient had an orthopantomogram (OPG) taken before the extraction and this showed an ill-defined radiolucent area in the periapical region of 41, 42 and 43 (figure 2). An occlusal radiograph revealed the expansion of buccal cortical plate with irregular bone loss in the anterior region extending from premolar region on the right side to the incisor region of the left side of the mandible (figure 3).

Figure 2.

OPG taken before extraction showing an ill-defined radiolucency in the periapical area of 41, 42 and 43. OPG, orthopantomogram.

Figure 3.

Occlusal radiograph showing expansion of the buccal cortical plate with irregular bone loss in the anterior region extending from the premolar region on the right side to the incisor region of the left side of the mandible.

Differential diagnosis

• Osteomyelitis since the patient had a history of carious teeth and pain.

• Primary intraosseous carcinoma either of odontogenic or salivary gland origin.

• Osteosarcoma was also considered possible because the radiograph showed the expansion of the cortical plate with ill-defined bone loss.

• Metastatic malignancies as the patient had numb chin syndrome.

• Solitary plasmacytoma/multiple myeloma.

Treatment

An incisional biopsy was done and multiple hard and soft tissue specimens were sent for histopathological examination. Microscopic examination showed sections with fragments of bone and scanty soft tissue composed of strands of atypical epithelial cells showing large hyperchromatic pleomorphic nucleus with abundant eosinophilic cytoplasm (figure 4). Some of them showed attempted duct formation but no secretary material was noted (figure 5). Some cells were also grouped in nests. These features led us to make a diagnosis of malignant neoplasm possibly adenocarcinoma. Adenocarcinoma arising centrally within the mandible, from entrapped salivary gland and metastatic adenocarcinoma, are adenocarcinomas probable in this region. To rule out metastatic adenocarcinoma, a whole body examination was advised. Chest X-rays and whole body Positron emission tomography (PET) scan were done. The chest X-ray showed a soft tissue density with cavitatory changes in the apical and posterior segments of the right lung upper lobe. The PET scan showed an increased FDG (fluorodeoxyglucose) uptake in various parts of the body like lungs, liver, kidneys, vertebrae, mandible, femur, sacrum and bilateral ribs indicating widespread lesion (figure 6). The scan was also positive for multiple nodal metastases. The lesion in the lung showed the highest uptake on the scan (figure 7) suggesting that this might be the primary lesion. Following this, immunohistochemical staining with thyroid transcription factor 1 (TTF-1) was done and was found to be positive for the tumour cells (figure 8). Co-relating TTF-1 positivity and PET scan showing highest uptake in the lungs with negative uptake in the thyroid, a final diagnosis of adenocarcinoma of lung stage IV with metastatic lesions to the mandible and to other body parts was made.

Figure 4.

Strands of atypical epithelial cells showing large hyperchromatic pleomorphic nucleus with abundant eosinophilic cytoplasm (H&E).

Figure 5.

Tumour cells showing attempted duct formation (H&E).

Figure 6.

The PET scan showing an increased FDG uptake in various parts of the body like lungs, liver, kidneys, vertebrae, mandible, femur, sacrum and bilateral ribs. FDG, fluorodeoxyglucose; PET, positron emission tomography.

Figure 7.

The lesion in the lung showed the highest uptake in PET scan. PET, positron emission tomography.

Figure 8.

Positive immunostaining with TTF-1. TTF-1, thyroid transcription factor 1.

The patient was then referred to the oncology department for further evaluation and treatment. She was given EGFR-targeted therapy (gefitinib) and also considered for palliative radiotherapy for the jaw pain due to the extensive nature of her disease.

Outcome and follow-up

During the course of radiotherapy, she developed pain in the hip region. Radiographs taken showed an osteolytic lesion in the left head of the femur. Hence, radiotherapy was given to the hip also for the relief of pain. Subsequent to the palliative radiotherapy, her pain was significantly reduced.

Ten months after gefitinib therapy, her chest radiographs showed a good response but developed a new lesion in the supraclavicular lymph node. Her general condition was poor with increased fatigue. She was subsequently referred for palliative care keeping in mind the widespread disease.

Discussion

Metastatic jaw tumours are exceedingly rare and are usually signs of a rather widespread disease process in the body.¹ Metastasis is a complex process occurring due to the presence of circulating tumour cells. These tumour cells may settle down and colonise at near or distant sites. This may occur later in the disease process or, in rare cases, early on.

Metastatic lesions are generally seen in older people. Oral metastases were the first evidence of metastatic dissemination in 25% of cases and also, were the first indication of a previously unknown malignant disease in 23% of patients.¹ These lesions occur more commonly in the jaw bones compared with the soft tissues with posterior mandible being the favoured site due to the presence of red marrow. In our case, unusually the anterior mandible was involved clinically rather than posterior. This could be explained by the fact that inflammation associated with the decayed tooth in this region resulted in the circulating tumour cells settling down here. When metastasis occurs in the soft tissues, gingiva is the preferred site alluding to the presence of inflammation in the area.^{1 2} Bone is a preferred site of metastasis of numerous types of solid neoplasms mainly the breast, prostate, thyroid gland, kidney and lungs.¹

A fast-growing bony expansion with paraesthesia is one of the common presentations of a metastatic lesion. The mucosa on the surface appears normal in colour and the patient may have an associated vague pain. ‘Numb chin’ syndrome is also a classical indicator and occurs either due to malignant infiltration of mental nerve or by compression of the nerve by tumour tissue. Some cases of metastatic jaw lesions may present with features similar to toothache, dental abscess, temporomandibular disorders, osteomyelitis or atypical neuralgia.³ These features may be misleading to the clinician. Radiographic examination usually shows an irregular lytic lesion or moth-eaten appearance indicative of a fast-growing pathology. Histopathological examination is the key to diagnosis. If the primary malignancy is known, the diagnosis is easier as the metastatic lesion will have the same histopathological picture as the primary. In cases of unknown primary, the diagnosis is difficult and use of adjunct methods like immunohistochemistry is essential for the final diagnosis along with whole body examination. TTF-1 positivity is seen in both adenocarcinomas of lung and thyroid. But, the absence of a lesion in the thyroid in the scan lead us to a diagnosis of primary lung adenocarcinoma. The immunohistochemical markers for identification of some of the unknown primary which commonly metastasizes to the oral cavity are given by Hirshberg et al ¹ and are summarised in table 1.

Table 1.

Immunohistochemical markers for unknown primary to oral cavity

Tissue of origin	Markers
Lung	CK 7+, CK 20−, TTF-1
Breast	CK 7+, CK 20−, GCDFP-15
Kidney	CK 7−, CK 20−, EMA, PAX 2
Thyroid	CK 7+, CK 20−, TTF-1, thyroglobulin
Colo-rectum	CK 7−, CK 20+, CEA, PAX 2

CK, cytokeratin; TTF-1, thyroid transcription factor 1.

Similar cases of unknown primary with a metastatic lesion in the mandible have been reported previously.^4–10 Most common symptoms reported were swelling and altered sensation.³ Multiple lesions in both jaws were reported in a case of metastatic bronchoalveolar carcinoma.⁴ The presence of systemic symptoms like cough may give a clue in the diagnosis of the primary lesion.⁷ Radiographically, ill-defined radiolucency or moth-eaten appearance was seen in cases of metastatic lung carcinomas while metastases from prostate and breast can show mixed radiolucent radio-opaque appearance.¹¹ A biopsy followed by whole-body examination was undertaken in all the cases for diagnosis.

In our case, since the presence of malignancy elsewhere in the body was not known and the patient had only the jaw complaint, the presence of a metastatic tumour was not considered as a primary diagnosis. Histopathological examination showed the presence of an adenocarcinoma. Since a metastatic lesion can present with a rapid swelling and altered sensation, it was decided to do a full body examination to locate the same. The presence of a widespread tumour limits the scope of curative therapy and the prognosis is usually poor, and the treatment becomes more focused on palliative care. Also, the presence of an oral metastatic disease gives the patient a grave prognosis as the mean survival rate from the appearance of a metastatic lesion to death is 7.3 months.¹²

Learning points.

• Metastatic jaw tumours, though comparatively rare, can mimic common odontogenic lesions like tooth abscess and osteomyelitis.

• In the presence of ‘numb chin’ syndrome, the possibility of a metastatic lesion cannot be discounted especially in the elderly and a thorough history taking is essential.

• Whole body examination is warranted in suspected cases.

• Histopathology is the key to diagnosis with appropriate selection of immunohistochemical markers.