- Email: [email protected]
Renal Cell Carcinoma Metastatic to the Tongue: A Case Report and Review of the Literature
Renal Cell Carcinoma Metastatic to the Tongue: A Case Report and Review of the Literature Ozan Altuntas¸, MD,* I_ brahim Petekkaya, MD,y Nilda S€ usl€ u, MD,z _ and I brahim G€ ull€ u, MDx Renal cell carcinoma (RCC) metastatic to the head and neck region is quite rare. This report describes a case of RCC metastatic to the oral tongue presenting initially with a renal mass that evaded diagnosis by biopsy examination of the primary lesion and was eventually established as a papillary type RCC by lingual biopsy examination. The tongue mass progressed rapidly despite chemotherapy with interferon-a2b, caused difficulties with oral food intake, and thus necessitated removal by partial glossectomy. Treatment alternatives for lingual RCC metastasis include surgical resection for major functional impairment, risk of airway compromise, or massive hemorrhage. Radiotherapy might be useful and should be considered for specific patients. Lingual metastasis from RCC usually predicts poor survival. Ó 2015 American Association of Oral and Maxillofacial Surgeons J Oral Maxillofac Surg 73:1227-1230, 2015 Metastatic lesions of the tongue are quite rare, with a reported incidence of 0.17%.1 Renal cell carcinoma (RCC) is a tumor of marked metastatic potential and the third tumor most commonly metastatic to the head and neck region, after breast and lung carcinomas. This report describes a case of RCC metastatic to the tongue presenting initially with a renal mass that evaded diagnosis by biopsy examination of the primary lesion and was eventually established as a papillary type RCC with multiple systemic metastases by lingual biopsy examination. The current diagnostic and therapeutic options are discussed in light of the recent literature.
Report of Case A 70-year-old male patient was referred to the authors’ department for an oral tongue mass of 6 months’ duration. The patient had a history of a steadily growing, occasionally hemorrhagic, lesion that restricted oral food intake. At physical examination, a 4-cm vegetative mass involving the right anterior two thirds of the dorsal tongue with palpable submucosal infiltration *Resident, Department of Otorhinolaryngology, Hacettepe University School of Medicine, Ankara, Turkey. yAttending Physician, Department of Oncology, Gaziantep Dr Ersin Arslan State Hospital, Gaziantep, Turkey.
was observed (Fig 1). Although the bulky lesion restricted tongue movements, hypoglossal nerve function was judged to be intact. There were no palpable lymph nodes in the neck and no other major finding was noted after a comprehensive ear, nose, and throat examination, including fiberoptic nasopharyngoscopy and laryngoscopy. Medical history disclosed a prior abdominal computed tomographic (CT) scan at another institution obtained for lumbar pain that had shown a heterogenous 13-cm mass with peripheral calcifications and contrast-enhancing solid components at the inferior pole of the right kidney, strongly suggestive of malignancy (Fig 2). Positron-emission tomographic (PET)-CT scan for possible metastases depicted multiple malignant or metastatic lesions in the 2 lungs, mediastinal lymph nodes, second lumbar vertebra, and right kidney. A renal percutaneous needle aspiration and Tru-Cut biopsy had been performed. Cytology showed necrotic debris, and histopathology showed only necrotic tissues with no trace of viable cells. An incisional biopsy of the oral tongue mass was performed. Specimens were obtained by cold knife Address correspondence and reprint requests to Dr Altuntas¸: € niversitesi, Tıp Fak€ Hacettepe U ultesi, Kulak Burun Bogaz Anabilim Dalı Sıhhiye, Ankara, T€ urkiye 06550; e-mail: [email protected] Received August 28 2014
zAssociate Professor, Department of Otorhinolaryngology,
Accepted December 23 2014
Hacettepe University School of Medicine, Ankara, Turkey.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
xProfessor, Department of Medical Oncology, Hacettepe University School of Medicine, Anakara, Turkey.
0278-2391/14/01855-2 http://dx.doi.org/10.1016/j.joms.2014.12.031
1227
1228
FIGURE 1. Lingual metastatic lesion at time of biopsy examination. A vegetative mass occupying the anterior two thirds of the right side of the tongue with marked submucosal infiltration can be observed. Altuntas¸ et al. Renal Cell Carcinoma Metastatic to the Tongue. J Oral Maxillofac Surg 2015.
dissection from the fragile, hemorrhagic mass. Pathologic examination showed a subepithelial neoplastic infiltration with alveolar, tubular, and papillary archi-
RENAL CELL CARCINOMA METASTATIC TO THE TONGUE
tecture that was diffusely positive for epithelial membrane antigen, vimentin, CK7, and RCC and focally positive for CD10 and 34BE12 at immunohistochemical staining. Antibodies directed toward RCC antigen are employed as an immunohistochemical stain. Pathologic diagnosis was papillary type RCC metastasis (Fig 3). Figure 3A presents tumoral infiltration under the lingual squamous epithelium. Figures 3B and C display the tubular and papillary architecture of the neoplasia. Figure 3D shows diffuse positive staining of the tumor with CK7. The patient was referred to the oncology department with these findings and received interferon-a2b treatment for 1 month, during which the tongue lesion progressed. He lost 12 kg owing to a restricted diet and was noted to have marked cachexia at follow-up examinations. Owing to a lack of response to interferon-a2b treatment, palliative resection of the lesion was planned. The patient underwent partial glossectomy with an uneventful recovery. Sunitinib therapy (50 mg/day) was initiated postoperatively. At the time of this writing, the patient was under follow-up with sunitinib therapy, 7 months after the initial diagnosis by tongue biopsy examination.
FIGURE 2. Computed tomographic section of renal mass. A 13-cm mass with peripheral calcifications (arrow) is present at the inferior pole of the right kidney. Altuntas¸ et al. Renal Cell Carcinoma Metastatic to the Tongue. J Oral Maxillofac Surg 2015.
1229
ALTUNTAS¸ ET AL
FIGURE 3. Histopathology of resected metastatic lesion. A, Renal cell carcinoma infiltration beneath the lingual squamous epithelium in hematoxylin and eosin (H&E) staining. B, C, Papillary and tubular tumoral architecture in H&E staining. D, Diffuse positive immunohistochemical staining with CK7. Altuntas¸ et al. Renal Cell Carcinoma Metastatic to the Tongue. J Oral Maxillofac Surg 2015.
Discussion More than 90% of oral cavity cancers are squamous cell carcinomas, with most other lesions being of minor salivary gland origin. Metastatic tumors of the tongue were found to have an incidence of 0.17% in a series of 6,881 autopsy cases of malignant disease by Zegarelli et al.1 A lingual metastasis should be considered in patients presenting with a tongue mass with a history of concurrent or prior metastatic malignancy, particularly of tumors that have a tendency to metastasize to un-
usual sites, such as RCC. RCC is the third most common malignancy to metastasize to the head and neck region, after lung and breast carcinomas. Thirty to 40% of patients with RCC present with metastatic disease2 and the high metastatic potential accounts for the unpredictable clinical behavior of this malignancy. Head and neck metastasis is the presenting complaint in 7.5% of patients with RCC.3 An exhaustive review of the literature showed 29 reported cases of lingual RCC metastasis from 1911 to 2014.
1230
RENAL CELL CARCINOMA METASTATIC TO THE TONGUE
Proposed mechanisms for RCC metastasis involve the arterial, venous, or lymphatic circulation. Head and neck metastasis is commonly associated with lung involvement, although the Batson (paravertebral) venous plexus can provide a route for distant spread to the head and neck in the absence of pulmonary metastases. This valveless network of venous anastomoses theoretically poses less resistance to tumor emboli, allowing retrograde flow from the abdominal cavity. Ipsilateral cervical lymph node involvement was reported in a single case by Basely et al.4 The present case had no palpable lymph nodes in the neck region, although a PET-CT scan visualized nodal disease in the mediastinum. Common presenting symptoms include a rapidly growing mass that often causes hemorrhage. TorresCarranza et al5 described a tongue lesion that remarkably doubled in size during a period of 2 weeks. A common feature in the literature is the propensity of the lesions to bleed, which can complicate surgical procedures, presumably owing to the highly vascular nature of this tumor. Other symptoms can vary in accordance with the sites of metastasis, which can include the nose and paranasal sinuses, larynx, mandible, temporal bones, and thyroid and parathyroid glands.6 The present patient had a mass exhibiting steady growth and occasional bleeding, yet surgery was performed with relatively minor hemorrhage that was readily controlled with cautery. Diagnosis was made with clinical suspicion confirmed by an incisional biopsy examination. The literature recommends the use of fluorodeoxyglucose PET scanning, particularly in the surveillance of patients after nephrectomy and in restaging when evaluating visceral, nodal, or bony disease.4 Histopathologic features of RCC vary according to subtype. The clear cell type poses the most noteworthy diagnostic challenge, because it should be differentiated from clear cell malignancy of salivary gland origin by immunohistochemistry in the setting of an oral lesion.7,8 The present specimen was reported as papillary RCC based on diffuse positive staining with markers such as EMA, vimentin, CK7, and RCC. Treatment alternatives include palliative surgical resection of the lesion with or without adjuvant therapy. Most cases in the literature were treated with palliative resection of the lingual lesion by simple amputation of the mass or partial glossectomy, presumably depending on the extent of submucosal invasion. Nephrectomy had been performed for the primary tumor in a multitude of cases, because an initial presentation with a metastatic lesion was quite rare. Adjuvant chemotherapy might be indicated for treatment.9 The present patient had multiple systemic metastases refractory to interferon-a2b administration, necessitating a relatively newer chemotherapeutic agent, sunitinib. RCC is classically regarded as
a radioresistant tumor, yet there are reports in the literature advocating the use of palliative radiation for RCC metastases. Tomita et al10 used a 50-Gy course that induced temporary regression of a tongue lesion. In the authors’ opinion, in a case with major functional impairment, such as an inability to tolerate food intake, or impending airway compromise owing to lesion bulk or probable hemorrhage, palliative resection is indicated for the metastatic oral lesion. The major risk of major blood loss during surgery and preservation of tongue function to the greatest extent possible are points for concern. Median survival in the setting of RCC metastasis to the tongue has been reported to be 5.8 months.11 Systemic metastases to vital organs, such as lung metastases, rather than lingual lesions define survival. Airway obstruction or massive hemorrhage can cause mortality owing to an oral metastasis. RCC is a tumor of considerable metastatic potential to the head and neck region and should be considered in the differential diagnosis of a secondary lingual tumor. Such patients tend to have multiple systemic metastases that might define survival. Alternatives for local control include surgical resection for cases with major functional impairment, risk of airway compromise, or massive hemorrhage. Radiotherapy could be useful and should be considered for specific patients. Lingual metastasis from RCC usually predicts poor survival.
References 1. Zegarelli DJ, Tsukada Y, Pickren JW, et al: Metastatic tumor to the tongue. Report of twelve cases. Oral Surg Oral Med Oral Pathol 35:202, 1973 2. Marioni G, Gaio E, Poletti A, et al: Uncommon metastatic site of renal adenocarcinoma: The oral tongue. Acta Otolaryngol 124: 197, 2004 3. Pritchyk KM, Schiff BA, Newkirk KA, et al: Metastatic renal cell carcinoma to the head and neck. Laryngoscope 112:1598, 2002 4. Basely M, Bonnel S, Maszelin P, et al: A rare presentation of metastatic renal clear cell carcinoma to the tongue seen on FDG PET. Clin Nucl Med 34:566, 2009 5. Torres-Carranza E, Garcia-Perla A, Infante-Cossio P, et al: Airway obstruction due to metastatic renal cell carcinoma to the tongue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:e76, 2006 6. Lang E, Patil N, Walsh R, et al: A case of renal cell carcinoma metastatic to the nose and tongue. Ear Nose Throat J 82:382, 2003 7. Corsi A, Guerra F, Grippaudo G, et al: Oral metastasis of renal cell carcinoma. Report of case and critical evaluation of morphologic features for differential diagnosis. Pathologica 86:665, 1994 8. Abbaszadeh-Bidokhty H, Motallebnejad M, Rajabi-Moghaddam M: Metastatic renal cell carcinoma presenting as a clear-cell tumor in tongue: A case report. Iran J Otorhinolaryngol 26:185, 2014 9. Paiva MB, Sercarz JA, Pantuck AJ, et al: Combined cytoreductive laser therapy and immunotherapy for palliation of metastatic renal cell carcinoma to the head and neck. Lasers Med Sci 22: 60, 2007 10. Tomita T, Inouye T, Shinden S, et al: Palliative radiotherapy for lingual metastasis of renal cell carcinoma. Auris Nasus Larynx 25:209, 1998 11. Azam F, Abubakerr M, Gollins S: Tongue metastasis as an initial presentation of renal cell carcinoma: A case report and literature review. J Med Case Rep 2:249, 2008
Report of Case A 70-year-old male patient was referred to the authors’ department for an oral tongue mass of 6 months’ duration. The patient had a history of a steadily growing, occasionally hemorrhagic, lesion that restricted oral food intake. At physical examination, a 4-cm vegetative mass involving the right anterior two thirds of the dorsal tongue with palpable submucosal infiltration *Resident, Department of Otorhinolaryngology, Hacettepe University School of Medicine, Ankara, Turkey. yAttending Physician, Department of Oncology, Gaziantep Dr Ersin Arslan State Hospital, Gaziantep, Turkey.
was observed (Fig 1). Although the bulky lesion restricted tongue movements, hypoglossal nerve function was judged to be intact. There were no palpable lymph nodes in the neck and no other major finding was noted after a comprehensive ear, nose, and throat examination, including fiberoptic nasopharyngoscopy and laryngoscopy. Medical history disclosed a prior abdominal computed tomographic (CT) scan at another institution obtained for lumbar pain that had shown a heterogenous 13-cm mass with peripheral calcifications and contrast-enhancing solid components at the inferior pole of the right kidney, strongly suggestive of malignancy (Fig 2). Positron-emission tomographic (PET)-CT scan for possible metastases depicted multiple malignant or metastatic lesions in the 2 lungs, mediastinal lymph nodes, second lumbar vertebra, and right kidney. A renal percutaneous needle aspiration and Tru-Cut biopsy had been performed. Cytology showed necrotic debris, and histopathology showed only necrotic tissues with no trace of viable cells. An incisional biopsy of the oral tongue mass was performed. Specimens were obtained by cold knife Address correspondence and reprint requests to Dr Altuntas¸: € niversitesi, Tıp Fak€ Hacettepe U ultesi, Kulak Burun Bogaz Anabilim Dalı Sıhhiye, Ankara, T€ urkiye 06550; e-mail: [email protected] Received August 28 2014
zAssociate Professor, Department of Otorhinolaryngology,
Accepted December 23 2014
Hacettepe University School of Medicine, Ankara, Turkey.
Ó 2015 American Association of Oral and Maxillofacial Surgeons
xProfessor, Department of Medical Oncology, Hacettepe University School of Medicine, Anakara, Turkey.
0278-2391/14/01855-2 http://dx.doi.org/10.1016/j.joms.2014.12.031
1227
1228
FIGURE 1. Lingual metastatic lesion at time of biopsy examination. A vegetative mass occupying the anterior two thirds of the right side of the tongue with marked submucosal infiltration can be observed. Altuntas¸ et al. Renal Cell Carcinoma Metastatic to the Tongue. J Oral Maxillofac Surg 2015.
dissection from the fragile, hemorrhagic mass. Pathologic examination showed a subepithelial neoplastic infiltration with alveolar, tubular, and papillary archi-
RENAL CELL CARCINOMA METASTATIC TO THE TONGUE
tecture that was diffusely positive for epithelial membrane antigen, vimentin, CK7, and RCC and focally positive for CD10 and 34BE12 at immunohistochemical staining. Antibodies directed toward RCC antigen are employed as an immunohistochemical stain. Pathologic diagnosis was papillary type RCC metastasis (Fig 3). Figure 3A presents tumoral infiltration under the lingual squamous epithelium. Figures 3B and C display the tubular and papillary architecture of the neoplasia. Figure 3D shows diffuse positive staining of the tumor with CK7. The patient was referred to the oncology department with these findings and received interferon-a2b treatment for 1 month, during which the tongue lesion progressed. He lost 12 kg owing to a restricted diet and was noted to have marked cachexia at follow-up examinations. Owing to a lack of response to interferon-a2b treatment, palliative resection of the lesion was planned. The patient underwent partial glossectomy with an uneventful recovery. Sunitinib therapy (50 mg/day) was initiated postoperatively. At the time of this writing, the patient was under follow-up with sunitinib therapy, 7 months after the initial diagnosis by tongue biopsy examination.
FIGURE 2. Computed tomographic section of renal mass. A 13-cm mass with peripheral calcifications (arrow) is present at the inferior pole of the right kidney. Altuntas¸ et al. Renal Cell Carcinoma Metastatic to the Tongue. J Oral Maxillofac Surg 2015.
1229
ALTUNTAS¸ ET AL
FIGURE 3. Histopathology of resected metastatic lesion. A, Renal cell carcinoma infiltration beneath the lingual squamous epithelium in hematoxylin and eosin (H&E) staining. B, C, Papillary and tubular tumoral architecture in H&E staining. D, Diffuse positive immunohistochemical staining with CK7. Altuntas¸ et al. Renal Cell Carcinoma Metastatic to the Tongue. J Oral Maxillofac Surg 2015.
Discussion More than 90% of oral cavity cancers are squamous cell carcinomas, with most other lesions being of minor salivary gland origin. Metastatic tumors of the tongue were found to have an incidence of 0.17% in a series of 6,881 autopsy cases of malignant disease by Zegarelli et al.1 A lingual metastasis should be considered in patients presenting with a tongue mass with a history of concurrent or prior metastatic malignancy, particularly of tumors that have a tendency to metastasize to un-
usual sites, such as RCC. RCC is the third most common malignancy to metastasize to the head and neck region, after lung and breast carcinomas. Thirty to 40% of patients with RCC present with metastatic disease2 and the high metastatic potential accounts for the unpredictable clinical behavior of this malignancy. Head and neck metastasis is the presenting complaint in 7.5% of patients with RCC.3 An exhaustive review of the literature showed 29 reported cases of lingual RCC metastasis from 1911 to 2014.
1230
RENAL CELL CARCINOMA METASTATIC TO THE TONGUE
Proposed mechanisms for RCC metastasis involve the arterial, venous, or lymphatic circulation. Head and neck metastasis is commonly associated with lung involvement, although the Batson (paravertebral) venous plexus can provide a route for distant spread to the head and neck in the absence of pulmonary metastases. This valveless network of venous anastomoses theoretically poses less resistance to tumor emboli, allowing retrograde flow from the abdominal cavity. Ipsilateral cervical lymph node involvement was reported in a single case by Basely et al.4 The present case had no palpable lymph nodes in the neck region, although a PET-CT scan visualized nodal disease in the mediastinum. Common presenting symptoms include a rapidly growing mass that often causes hemorrhage. TorresCarranza et al5 described a tongue lesion that remarkably doubled in size during a period of 2 weeks. A common feature in the literature is the propensity of the lesions to bleed, which can complicate surgical procedures, presumably owing to the highly vascular nature of this tumor. Other symptoms can vary in accordance with the sites of metastasis, which can include the nose and paranasal sinuses, larynx, mandible, temporal bones, and thyroid and parathyroid glands.6 The present patient had a mass exhibiting steady growth and occasional bleeding, yet surgery was performed with relatively minor hemorrhage that was readily controlled with cautery. Diagnosis was made with clinical suspicion confirmed by an incisional biopsy examination. The literature recommends the use of fluorodeoxyglucose PET scanning, particularly in the surveillance of patients after nephrectomy and in restaging when evaluating visceral, nodal, or bony disease.4 Histopathologic features of RCC vary according to subtype. The clear cell type poses the most noteworthy diagnostic challenge, because it should be differentiated from clear cell malignancy of salivary gland origin by immunohistochemistry in the setting of an oral lesion.7,8 The present specimen was reported as papillary RCC based on diffuse positive staining with markers such as EMA, vimentin, CK7, and RCC. Treatment alternatives include palliative surgical resection of the lesion with or without adjuvant therapy. Most cases in the literature were treated with palliative resection of the lingual lesion by simple amputation of the mass or partial glossectomy, presumably depending on the extent of submucosal invasion. Nephrectomy had been performed for the primary tumor in a multitude of cases, because an initial presentation with a metastatic lesion was quite rare. Adjuvant chemotherapy might be indicated for treatment.9 The present patient had multiple systemic metastases refractory to interferon-a2b administration, necessitating a relatively newer chemotherapeutic agent, sunitinib. RCC is classically regarded as
a radioresistant tumor, yet there are reports in the literature advocating the use of palliative radiation for RCC metastases. Tomita et al10 used a 50-Gy course that induced temporary regression of a tongue lesion. In the authors’ opinion, in a case with major functional impairment, such as an inability to tolerate food intake, or impending airway compromise owing to lesion bulk or probable hemorrhage, palliative resection is indicated for the metastatic oral lesion. The major risk of major blood loss during surgery and preservation of tongue function to the greatest extent possible are points for concern. Median survival in the setting of RCC metastasis to the tongue has been reported to be 5.8 months.11 Systemic metastases to vital organs, such as lung metastases, rather than lingual lesions define survival. Airway obstruction or massive hemorrhage can cause mortality owing to an oral metastasis. RCC is a tumor of considerable metastatic potential to the head and neck region and should be considered in the differential diagnosis of a secondary lingual tumor. Such patients tend to have multiple systemic metastases that might define survival. Alternatives for local control include surgical resection for cases with major functional impairment, risk of airway compromise, or massive hemorrhage. Radiotherapy could be useful and should be considered for specific patients. Lingual metastasis from RCC usually predicts poor survival.
References 1. Zegarelli DJ, Tsukada Y, Pickren JW, et al: Metastatic tumor to the tongue. Report of twelve cases. Oral Surg Oral Med Oral Pathol 35:202, 1973 2. Marioni G, Gaio E, Poletti A, et al: Uncommon metastatic site of renal adenocarcinoma: The oral tongue. Acta Otolaryngol 124: 197, 2004 3. Pritchyk KM, Schiff BA, Newkirk KA, et al: Metastatic renal cell carcinoma to the head and neck. Laryngoscope 112:1598, 2002 4. Basely M, Bonnel S, Maszelin P, et al: A rare presentation of metastatic renal clear cell carcinoma to the tongue seen on FDG PET. Clin Nucl Med 34:566, 2009 5. Torres-Carranza E, Garcia-Perla A, Infante-Cossio P, et al: Airway obstruction due to metastatic renal cell carcinoma to the tongue. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 101:e76, 2006 6. Lang E, Patil N, Walsh R, et al: A case of renal cell carcinoma metastatic to the nose and tongue. Ear Nose Throat J 82:382, 2003 7. Corsi A, Guerra F, Grippaudo G, et al: Oral metastasis of renal cell carcinoma. Report of case and critical evaluation of morphologic features for differential diagnosis. Pathologica 86:665, 1994 8. Abbaszadeh-Bidokhty H, Motallebnejad M, Rajabi-Moghaddam M: Metastatic renal cell carcinoma presenting as a clear-cell tumor in tongue: A case report. Iran J Otorhinolaryngol 26:185, 2014 9. Paiva MB, Sercarz JA, Pantuck AJ, et al: Combined cytoreductive laser therapy and immunotherapy for palliation of metastatic renal cell carcinoma to the head and neck. Lasers Med Sci 22: 60, 2007 10. Tomita T, Inouye T, Shinden S, et al: Palliative radiotherapy for lingual metastasis of renal cell carcinoma. Auris Nasus Larynx 25:209, 1998 11. Azam F, Abubakerr M, Gollins S: Tongue metastasis as an initial presentation of renal cell carcinoma: A case report and literature review. J Med Case Rep 2:249, 2008