Australian Dental Journal
The official journal of the Australian Dental Association
Australian Dental Journal 2014; 59: 520–524 doi: 10.1111/adj.12215
Non-small cell lung cancer metastasis to the oral cavity: a case report JB Olsen,* F Sim,* A Chandu* *Department of Oral and Maxillofacial Surgery, Western Hospital Footscray, Victoria.
ABSTRACT Lung cancer, including non-small cell lung cancer, remains prevalent in Australia and has a very poor survival rate. Metastases to the oral cavity are a rare occurrence that can arise from lung cancers. This case report describes the presentation of a metastatic lesion from a poorly differentiated lung adenocarcinoma on the mandibular buccal alveolar attached gingivae. The inpatient had terminal disease with known pleural, brain and liver metastases and was receiving palliative care at the time of diagnosis of the oral lesion. Keywords: Adenocarcinoma, cancer, oral metastasis. Abbreviations and acronyms: ALK = anaplastic lymphoma kinase; CT = computed tomography; EBUS = endobronchial ultrasound scan; EGFR = epidermal growth factor receptor; IHC = immunohistochemistry; MRI = magnetic resonance imaging; NSCLC = non-small cell lung cancer. (Accepted for publication 17 March 2014.)
INTRODUCTION Metastasis of malignant tumours to the oral cavity is relatively rare and particularly those confined to the oral soft tissues are very uncommon.1 Although rare however, oral metastases have diagnostic (a quarter of them reveal an unknown cancer) and prognostic significance (their presence is correlated with limited survival of the patients).2 CASE DESCRIPTION A 42-year-old male presented to his general medical practitioner with a complaint of right shoulder pain. He worked in the shipping industry and had moved to Australia from Singapore a few years previously. When a provisional diagnosis of musculoskeletal pain and a brief trial period of initial physiotherapy and oral non-steroidal anti-inflammatory agents failed to control his pain, he was referred to the Western Hospital Footscray emergency department for further investigation. A chest radiograph and subsequent computed tomography (CT) scan taken at this time revealed a right upper lobe lung mass (Fig. 1). An urgent bronchoscopy was performed, which revealed a Pancoast tumour in the right upper lobe. Initial biopsy was unsuccessful in yielding viable tissue for diagnosis, and so the patient was re-booked the 520
Fig. 1 Coronal contrast enhanced CT of the chest confirms a rounded soft tissue mass in the right apex with probable right hilar nodal metastasis.
following week for an endobronchial ultrasound scan (EBUS) and repeat biopsy. Unfortunately, the EBUS also failed to obtain any tissue for diagnosis; however, © 2014 Australian Dental Association
Metastatic oral small cell lung cancer it did visualize enlarged hilar lymph nodes, suggesting the possibility of invasive disease. In view of this, full staging with magnetic resonance imaging (MRI) of the brain, chest, abdomen and pelvis as well as positron emission tomography was conducted. The MRI scans confirmed the presence of probable metastatic foci in the liver, brain (frontal, parietal and cerebellar lesions as demonstrated in Figs. 2, 3 and 4 respectively) and pleural cavity. Due to previous failed attempts to obtain diagnostic tissue from his lung, the patient underwent two separate craniotomies for resection of metastatic foci from the cerebellar and cerebral lesions. This was performed to obtain tissue for a definitive diagnosis. Following the procedure, the patient underwent whole brain radiotherapy. Histopathology of the tissue sample confirmed the diagnosis of adenocarcinoma; various stains were performed to make the diagnosis. After confirmation of diagnosis, the patient received six cycles of targeted chemotherapy as well as local radiation therapy to the chest. The tumour was epidermal growth factor receptor (EGFR) negative and anaplastic lymphoma kinase (ALK) was not detected. A chemotherapeutic regime of Carboplatin and Paclitaxel was selected on this basis. Fig. 3 Axial T1 post contrast MRI imaging of the brain demonstrates heterogeneously enhancing, slightly lobulated intra axial masses in the parietal lobe.
Fig. 2 Axial T1 post contrast MRI imaging of the brain demonstrates heterogeneously enhancing, slightly lobulated intra axial masses in the right frontal lobe. © 2014 Australian Dental Association
Unfortunately following this treatment, the patient presented to the emergency department complaining of shortness of breath, pleuritic chest pain, nausea, fevers and a new mass on his lower anterior gingiva (Fig. 5). A referral was made to the Oral and Maxillofacial Surgery Unit for investigation and management of the gingival mass. The history of this lesion was of self-reported rapid growth over two weeks to the point that it interfered with his mastication, causing bleeding and pain. Examination revealed a 15 mm x 15 mm firm lesion, arising from the interdental papilla between teeth 32 and 33. This lesion was pedunculated and firm to palpate. There was no mobility of the associated teeth and the floor of mouth was unremarkable. A lesion was excised without complication under local anaesthesia and sent for histopathological examination. The histopathology from the specimen was reported initially as malignant undifferentiated tumour, morphology consistent with large cell carcinoma/poorly differentiated adenocarcinoma. The tumour extended beyond the base of the resected margin. Sections were subsequently stained with immunoperoxidase and cells were positive for CKAE1/AE3, 34 beta E12, CK7, Ber-EP4 (Fig. 6), polyclonal CEA 521
JB Olsen et al.
Fig. 6 BerEP4 stain, x200 magnification. Tumour cells with positive membrane staining. A positive stain for BerEP4 is more consistent with adenocarcinoma and less likely to indicate mesothelioma.
Fig. 4 Axial T1 post contrast MRI imaging of the brain demonstrates heterogeneously enhancing, slightly lobulated intra axial masses in the left cerebellar hemisphere.
Fig. 5 Pedunculated mass visible on labial mandibular attached gingivae.
and calretinin. The tumour was also stained with PAS diastase to search for mucin production. The overall features favoured adenocarcinoma, and this was compared with the previous slides taken from the left cerebellar metastasis. This changed the diagnosis to definitive, poorly differentiated adenocarcinoma. The role of immunohistochemistry (IHC) is vital to aid in diagnosis for cases such as this. The acronym 522
CKAE1/AE3 listed above stands for cytokeratin types AE1/AE3. This stain was used to confirm the epithelial nature of the tumour and search for metastatic carcinoma in any lymph tissue included within the biopsy. It also helped to assess the depth of local invasion. 34 beta E12 is another cytokeratin that when present can be used to exclude prostate adenocarcinoma. A further cytokeratin, CK7, is used to add weight to the diagnosis of a primary lung adenocarcinoma, although it is not exclusive to this tissue. BerEP4, listed above, is an antibody used to reliably label lung adenocarcinoma but will not normally label mesothelioma. Polyclonal carcinoembryonic antigen (polyclonal CEA) is produced in the majority of pulmonary adenocarcinomas. Mesotheliomas by contrast are rarely CEA positive. The final stain listed above was for the presence of calretinin. This is expressed in some lung adenocarcinomas and adds weight to the diagnosis. So the process of IHC can be employed to aid or reject the histopathological diagnosis through the recognition of various proteins and antigens expressed within the biopsy specimen. The respiratory symptoms at this time were presumed to be due to CT proven pleural invasion of tumour with resulting effusion in the right lung. The pleural effusion was drained via a pleuritic tap, the results of which prompted cessation of the chemotherapeutic regime and introduction of second line therapy with Pemetrexed. The first cycle was completed and tolerated well; unfortunately, the patient began to deteriorate during the second cycle. Family discussions were held at this time and the decision was made to cease chemotherapy and palliate the patient with symptom control and management. He continued to decline and within a few weeks passed away from complications related to his multiple liver metastases. © 2014 Australian Dental Association
Metastatic oral small cell lung cancer DISCUSSION Lung cancer is the leading cause of all cancer related deaths worldwide and the second most common cancer in both males and females.3 It is considered a terminal illness with a five-year survival rate of about 16%4 and this is despite significant advances in chemotherapeutic regimes. Of all lung cancers, approximately 80% are classified as nonsmall cell lung cancer (NSCLC), and approximately two-thirds of these patients will present with disease that is locally advanced and not amenable to curable surgery.5 Metastases to the oral cavity are a rare but significant complication of many cancers. Retrospective analyses of head and neck metastases have demonstrated that metastatic cancer from any primary site makes up about 1% of overall oral malignancies.6 Previously reported sites of primary lesions include breast, colorectum, kidney, female reproductive system, male reproductive system, thyroid, endocrine system, lung, as well as unknown or occult primaries. A case of maxillary metastatic hepatocellular carcinoma was recently reported in the Australian Dental Journal.7 Metastatic sites within the head and neck area also vary, with target tissue for metastatic bony disease having been reported in the maxilla, mandible and temporomandibular joint. With respect to soft tissue disease, the most common site for metastasis is the attached gingiva (57%), followed by the tongue (27%), tonsil (8%), palate (4%), lip (3%), buccal mucosa (1%) and floor of mouth (
The official journal of the Australian Dental Association
Australian Dental Journal 2014; 59: 520–524 doi: 10.1111/adj.12215
Non-small cell lung cancer metastasis to the oral cavity: a case report JB Olsen,* F Sim,* A Chandu* *Department of Oral and Maxillofacial Surgery, Western Hospital Footscray, Victoria.
ABSTRACT Lung cancer, including non-small cell lung cancer, remains prevalent in Australia and has a very poor survival rate. Metastases to the oral cavity are a rare occurrence that can arise from lung cancers. This case report describes the presentation of a metastatic lesion from a poorly differentiated lung adenocarcinoma on the mandibular buccal alveolar attached gingivae. The inpatient had terminal disease with known pleural, brain and liver metastases and was receiving palliative care at the time of diagnosis of the oral lesion. Keywords: Adenocarcinoma, cancer, oral metastasis. Abbreviations and acronyms: ALK = anaplastic lymphoma kinase; CT = computed tomography; EBUS = endobronchial ultrasound scan; EGFR = epidermal growth factor receptor; IHC = immunohistochemistry; MRI = magnetic resonance imaging; NSCLC = non-small cell lung cancer. (Accepted for publication 17 March 2014.)
INTRODUCTION Metastasis of malignant tumours to the oral cavity is relatively rare and particularly those confined to the oral soft tissues are very uncommon.1 Although rare however, oral metastases have diagnostic (a quarter of them reveal an unknown cancer) and prognostic significance (their presence is correlated with limited survival of the patients).2 CASE DESCRIPTION A 42-year-old male presented to his general medical practitioner with a complaint of right shoulder pain. He worked in the shipping industry and had moved to Australia from Singapore a few years previously. When a provisional diagnosis of musculoskeletal pain and a brief trial period of initial physiotherapy and oral non-steroidal anti-inflammatory agents failed to control his pain, he was referred to the Western Hospital Footscray emergency department for further investigation. A chest radiograph and subsequent computed tomography (CT) scan taken at this time revealed a right upper lobe lung mass (Fig. 1). An urgent bronchoscopy was performed, which revealed a Pancoast tumour in the right upper lobe. Initial biopsy was unsuccessful in yielding viable tissue for diagnosis, and so the patient was re-booked the 520
Fig. 1 Coronal contrast enhanced CT of the chest confirms a rounded soft tissue mass in the right apex with probable right hilar nodal metastasis.
following week for an endobronchial ultrasound scan (EBUS) and repeat biopsy. Unfortunately, the EBUS also failed to obtain any tissue for diagnosis; however, © 2014 Australian Dental Association
Metastatic oral small cell lung cancer it did visualize enlarged hilar lymph nodes, suggesting the possibility of invasive disease. In view of this, full staging with magnetic resonance imaging (MRI) of the brain, chest, abdomen and pelvis as well as positron emission tomography was conducted. The MRI scans confirmed the presence of probable metastatic foci in the liver, brain (frontal, parietal and cerebellar lesions as demonstrated in Figs. 2, 3 and 4 respectively) and pleural cavity. Due to previous failed attempts to obtain diagnostic tissue from his lung, the patient underwent two separate craniotomies for resection of metastatic foci from the cerebellar and cerebral lesions. This was performed to obtain tissue for a definitive diagnosis. Following the procedure, the patient underwent whole brain radiotherapy. Histopathology of the tissue sample confirmed the diagnosis of adenocarcinoma; various stains were performed to make the diagnosis. After confirmation of diagnosis, the patient received six cycles of targeted chemotherapy as well as local radiation therapy to the chest. The tumour was epidermal growth factor receptor (EGFR) negative and anaplastic lymphoma kinase (ALK) was not detected. A chemotherapeutic regime of Carboplatin and Paclitaxel was selected on this basis. Fig. 3 Axial T1 post contrast MRI imaging of the brain demonstrates heterogeneously enhancing, slightly lobulated intra axial masses in the parietal lobe.
Fig. 2 Axial T1 post contrast MRI imaging of the brain demonstrates heterogeneously enhancing, slightly lobulated intra axial masses in the right frontal lobe. © 2014 Australian Dental Association
Unfortunately following this treatment, the patient presented to the emergency department complaining of shortness of breath, pleuritic chest pain, nausea, fevers and a new mass on his lower anterior gingiva (Fig. 5). A referral was made to the Oral and Maxillofacial Surgery Unit for investigation and management of the gingival mass. The history of this lesion was of self-reported rapid growth over two weeks to the point that it interfered with his mastication, causing bleeding and pain. Examination revealed a 15 mm x 15 mm firm lesion, arising from the interdental papilla between teeth 32 and 33. This lesion was pedunculated and firm to palpate. There was no mobility of the associated teeth and the floor of mouth was unremarkable. A lesion was excised without complication under local anaesthesia and sent for histopathological examination. The histopathology from the specimen was reported initially as malignant undifferentiated tumour, morphology consistent with large cell carcinoma/poorly differentiated adenocarcinoma. The tumour extended beyond the base of the resected margin. Sections were subsequently stained with immunoperoxidase and cells were positive for CKAE1/AE3, 34 beta E12, CK7, Ber-EP4 (Fig. 6), polyclonal CEA 521
JB Olsen et al.
Fig. 6 BerEP4 stain, x200 magnification. Tumour cells with positive membrane staining. A positive stain for BerEP4 is more consistent with adenocarcinoma and less likely to indicate mesothelioma.
Fig. 4 Axial T1 post contrast MRI imaging of the brain demonstrates heterogeneously enhancing, slightly lobulated intra axial masses in the left cerebellar hemisphere.
Fig. 5 Pedunculated mass visible on labial mandibular attached gingivae.
and calretinin. The tumour was also stained with PAS diastase to search for mucin production. The overall features favoured adenocarcinoma, and this was compared with the previous slides taken from the left cerebellar metastasis. This changed the diagnosis to definitive, poorly differentiated adenocarcinoma. The role of immunohistochemistry (IHC) is vital to aid in diagnosis for cases such as this. The acronym 522
CKAE1/AE3 listed above stands for cytokeratin types AE1/AE3. This stain was used to confirm the epithelial nature of the tumour and search for metastatic carcinoma in any lymph tissue included within the biopsy. It also helped to assess the depth of local invasion. 34 beta E12 is another cytokeratin that when present can be used to exclude prostate adenocarcinoma. A further cytokeratin, CK7, is used to add weight to the diagnosis of a primary lung adenocarcinoma, although it is not exclusive to this tissue. BerEP4, listed above, is an antibody used to reliably label lung adenocarcinoma but will not normally label mesothelioma. Polyclonal carcinoembryonic antigen (polyclonal CEA) is produced in the majority of pulmonary adenocarcinomas. Mesotheliomas by contrast are rarely CEA positive. The final stain listed above was for the presence of calretinin. This is expressed in some lung adenocarcinomas and adds weight to the diagnosis. So the process of IHC can be employed to aid or reject the histopathological diagnosis through the recognition of various proteins and antigens expressed within the biopsy specimen. The respiratory symptoms at this time were presumed to be due to CT proven pleural invasion of tumour with resulting effusion in the right lung. The pleural effusion was drained via a pleuritic tap, the results of which prompted cessation of the chemotherapeutic regime and introduction of second line therapy with Pemetrexed. The first cycle was completed and tolerated well; unfortunately, the patient began to deteriorate during the second cycle. Family discussions were held at this time and the decision was made to cease chemotherapy and palliate the patient with symptom control and management. He continued to decline and within a few weeks passed away from complications related to his multiple liver metastases. © 2014 Australian Dental Association
Metastatic oral small cell lung cancer DISCUSSION Lung cancer is the leading cause of all cancer related deaths worldwide and the second most common cancer in both males and females.3 It is considered a terminal illness with a five-year survival rate of about 16%4 and this is despite significant advances in chemotherapeutic regimes. Of all lung cancers, approximately 80% are classified as nonsmall cell lung cancer (NSCLC), and approximately two-thirds of these patients will present with disease that is locally advanced and not amenable to curable surgery.5 Metastases to the oral cavity are a rare but significant complication of many cancers. Retrospective analyses of head and neck metastases have demonstrated that metastatic cancer from any primary site makes up about 1% of overall oral malignancies.6 Previously reported sites of primary lesions include breast, colorectum, kidney, female reproductive system, male reproductive system, thyroid, endocrine system, lung, as well as unknown or occult primaries. A case of maxillary metastatic hepatocellular carcinoma was recently reported in the Australian Dental Journal.7 Metastatic sites within the head and neck area also vary, with target tissue for metastatic bony disease having been reported in the maxilla, mandible and temporomandibular joint. With respect to soft tissue disease, the most common site for metastasis is the attached gingiva (57%), followed by the tongue (27%), tonsil (8%), palate (4%), lip (3%), buccal mucosa (1%) and floor of mouth (
