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Delayed tongue necrosis simultaneous with bilateral osteoradionecrosis of the jaw secondary to head and neck irradiation
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Delayed tongue necrosis simultaneous with bilateral osteoradionecrosis of the jaw secondary to head and neck irradiation Marcos Martins Curi, DDS, MSc, PhD,a,b Camila Lopes Cardoso, DDS, MSc, PhD,a,b Anthony Froy Condezo Benites, DDS,c and Patrícia Martins Bueno, DDSc We present a rare case of massive tongue necrosis occurring simultaneously with bilateral osteoradionecrosis (ORN) of the jaw in a patient with a history of treatment, including surgery and postoperative radiotherapy, for a retromolar trigone carcinoma 8 years earlier. There is a distinct possibility that the extractions and administration of local anesthesia with a vasoconstrictor contributed to the onset of ORN; together, these events may have influenced the blood supply to the tongue. A glossectomy was performed after hyperbaric oxygen therapy. One month after the surgical procedure, the patient responded satisfactorily to the treatment, showing significant improvement in speech and oral food intake, as well as significant decrease in lingual pain. Although the simultaneous occurrence of these oral complications is rare, the practitioner must be aware of the factors that instigate ORN and compromise vasculature as well as the clinical signs of tongue necrosis. Additionally, the possibility of tongue necrosis secondary to irradiation of the head and neck should be taken into consideration when an irradiated patient undergoes tooth extractions under local anesthesia with agents containing epinephrine. (Oral Surg Oral Med Oral Pathol Oral Radiol 2016;-:e1-e5)
Tongue necrosis is a rare oral complication associated with irradiation of the head and neck region. This condition may attributed to a wide range of causes, including malignant tumors, use of a vasoconstrictor, severe hemorrhage, embolism, abscess of the floor of the mouth, syphilis, giant cell arteritis, chemotherapy, and previous head and neck radiotherapy.1-5 The tongue has a rich vascular supply, consisting mainly of the bilateral lingual, pharyngeal, and facial arteries, in addition to collateral circulation. Generally, when tongue necrosis is observed, it commonly affects one side of the tongue, mainly the tip or the anterior half.1-5 The base of the tongue is never involved. Few cases of bilateral tongue necrosis have been reported in the literature.1-5 There are no reports of tongue necrosis occurring simultaneously with osteoradionecrosis (ORN) of the jaw. Primary tumors of the tongue are common, whereas metastatic tumors rarely occur at this site. Squamous cell carcinoma (SCC) is the most frequent primary malignant neoplasm occurring at this site.6 Treatment for tongue cancer usually involves surgery to remove the cancer.6 Chemotherapy, radiation therapy, and targeted drug therapy may also be recommended, a
Department of Oral and Maxillofacial Surgery, Universidade do Sagrado Coração, Bauru, São Paulo, Brazil. b Department of Oral Surgery, Hospital Santa Catarina, São Paulo, Brazil. c Department of Oral Surgery, Universidade Sagrado Coração, Bauru, São Paulo, Brazil. Received for publication Jul 13, 2016; returned for revision Oct 5, 2016; accepted for publication Oct 8, 2016. Ó 2016 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2016.10.010
depending on other factors, including the type and stage of cancer, possible side effects, and overall health of the patient. Radical neck dissection with ligation of the external carotid artery in patients receiving radiotherapy of the head and neck region has been reported as a cause of unilateral tongue necrosis.6 A search of texts published until 2016 and included in the MEDLINE database was conducted using specific terms: “lingual necrosis,” “lingual infarction,” “tongue necrosis,” “tongue infarction,” “giant cell arteritis and tongue necrosis,” “lingual ischemia,” and “head and neck radiotherapy and lingual necrosis.” Among the search results, we found only three cases of tongue necrosis occurring after head and neck radiotherapy.5-7 Therefore, the purpose of this report was to delineate a case of massive tongue necrosis occurring simultaneously with bilateral ORN of the jaw in a patient with a history of surgery and postoperative radiotherapy for SCC of retromolar trigone.
CASE REPORT A 56-year-old male was referred by his oncologist physician for dysphagia caused by a painful, swollen, and discolored tongue. The patient had a medical history of treatment for SCC (T2 N2 M0) of the right retromolar trigone area with a combination of surgery (tumor resection/modified radical neck dissection) and postoperative fractionated radiotherapy (5 fractions/week; 2.0 Gy/fraction; 34 sessions) 8 years earlier. To obtain more information about the surgery, we contacted the head and neck surgeon, who informed us that the patient had received right radical neck dissection (lymph nodes levels II to IV) without ligation of the external carotid artery. A total of 68 Gy had been applied to the oral cavity and
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Fig. 1. A and B, Brownish-black discoloration, edema, and tenderness involving the anterior third of the tongue bilaterally upon initial evaluation with movement limitation that compromised the patient’s speech and deglutition. 56 Gy to the entire chain of cervical nodes. The patient completed treatment for head and neck cancer and attended all follow-up appointments. He had remained disease-free since the end of his treatment in 2008. His medical history was negative for vasoconstrictor use, syphilis, cardiac arrest, or embolization. The patient was not taking any medication. An initial oral examination revealed edema, tenderness, and bilateral, brownish-black discoloration involving the anterior third of the tongue, with movement limitation that compromised his speech and deglutition. This tongue tissue area was necrotic, without bleeding, and sharply demarcated. The mucosa of the posterior two-thirds of the tongue had a normal appearance. In addition to this tongue alteration, bilateral exposure of necrotic bone of the body of the mandible was detected during oral examination (Figures 1A and 1B). The patient had a dental history of bilateral multiple exodontia (first and second right and left molars), which had been performed by his dentist 12 months earlier. According to the dentist, the reason for dental extractions was caries caused by radiation. The surgical procedure had been performed with the patient under local anesthesia (three cartridges, lidocaine 2% with epinephrine 1:100,000), and there were no complications. According to the dentist, the surgical wound did not heal adequately, and soft tissue breakdown and bilateral necrotic bone exposure occurred 20 days after the surgery. The patient denied symptoms of fever, arthralgia, neurologic alterations, weight loss, visual disturbances, jaw claudication, or temporal tenderness. Hematologic examination results were within normal parameters (white blood cells: 3.8 kU/L, hemoglobin: 14.4 g/dL, hematocrit: 42.8%, platelet: 250 kU/L). The erythrocyte sedimentation rate and cross-reactive protein were within normal limit (15 mm/hr and 2.5 mg/L, respectively). Panoramic radiograph demonstrated irregular diffuse osteolysis affecting alveolar bone on both sides of the mandible’s body and teeth alveoli with delayed remodeling (Figure 2). Because there was a strong diagnostic hypothesis of tongue necrosis as a consequence of prior radiotherapy for head and neck cancer, a tongue biopsy was performed. The specimen revealed soft tissue necrosis without signs of malignancy. In light of the diagnosis, Horton syndrome (temporal arteritis) was excluded because claudication of the legs, localized headache, abnormal temporal artery with tenderness, and decreased pulse were not present, and the erythrocyte sedimentation rate was not higher than 50 mm/hr. A carotid Doppler examination of the neck arteries yielded normal findings. The patient refused to undergo a superficial
Fig. 2. Panoramic radiograph demonstrating irregular diffuse osteolysis affecting the alveolar bone of the mandible bilaterally. temporal artery biopsy. With regard to the clinical and radiologic findings of the bilateral bone exposure in the mandible, we considered the hypothesis of ORN of the jaw. The patient’s initial management started with hyperbaric oxygen therapy (30 sessions: 20 sessions before surgery and 10 sessions after surgery; 2.4 ATA; 90-minute session in a monoplace chamber). Subsequently, a glossectomy was performed with the patient under general anesthesia, resulting in secondary wound healing (Figure 3). Bilateral marginal bone resections were performed to treat ORN on both sides of the mandible. Microscopic examination of the tongue specimen revealed fibrous proliferation with extensive areas of hyalinization associated with obliterated blood vessel lumen. Microscopic examination of the bone specimens revealed necrotic bone associated with a nonspecific chronic inflammatory process and the presence of colonies of filamentous bacteria. These investigations confirmed the diagnosis of tongue necrosis and ORN caused by radiation therapy for head and neck cancer. One month after the surgical procedure, the patient responded satisfactorily to treatment with significant improvement in speech and oral food intake and decreased lingual pain. The tongue lesion and ORN of the jaw healed completely over a 6-month follow-up period (Figures 4A-4C).
DISCUSSION Tongue necrosis is generally rare and may be associated with a wide range of pathologies. Differential diagnosis in tongue necrosis should include malignancies (carcinoma, sarcomas, lymphomas, metastatic tumors);
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Fig. 3. Necrotic specimen of the tongue.
medication use (chemotherapy and vasopressin); cardiovascular problems (cardiac arrest, embolisms, hemorrhage); infectious diseases (syphilis and tuberculosis); systemic vasculitis disorders (giant cell arteritis); and chemotherapy and head and neck radiotherapy.1-7 Therefore, careful history taking and physical examination to determine the association with the signs and symptoms of tongue necrosis are essential for accurate and early diagnosis. Despite the fact that the tongue is a well-vascularized anatomic site, there are reports of unilateral lingual necrosis that usually involves its anterior half. However, there are some cases of bilateral involvement reported in the literature.1-7 The current case presented bilateral tongue necrosis involving the anterior third of the tongue in a patient with a history of radiation therapy (8 years earlier) for SCC of the right retromolar trigone area and bilateral multiple exodontias performed using a local anesthetic containing a vasoconstrictor. The rarity of tongue necrosis caused by irradiation of the head and neck region is obvious, as indicated by the search conducted on this subject revealing only the three cases reported in the literature.5-7 The tongue is a common anatomic site of occurrence of malignant primary tumors and a less frequent site of involvement by metastatic tumors.8 The combination of surgery and postoperative radiotherapy is the standard treatment for SCC of the tongue in the advanced stage.8 Advanced tongue SCC (T3 and T4) often
CASE REPORT Curi et al. e3
requires neck dissection.8 Radical neck dissection with ligation of the external carotid artery in patients who had received postoperative radiotherapy to the head and neck has been reported as a possible cause of tongue necrosis.1-7 Postoperative radiotherapy usually includes the primary site and both sides of the neck, regardless of its indication being related to the primary tumor or metastases. Our patient had a medical history of surgery (tumor resection/modified radical neck dissection) and postoperative radiotherapy for oral cancer. In the literature, there is a scarcity of clinical studies on the evaluation of radiation tissue injury in humans. Although it is known that the higher the total doses used in the treatment of head and neck tumors, the greater the tissue adverse effects, there is still uncertainty about the pathophysiology of irradiated tissue injury. The basic pathophysiology of irradiation tissue injury is normal tissue cell death and sublethal normal tissue cell damage, leading to a wound-healing defect. Marx9 proposed the concept of hypovascular, hypocellular, and hypoxic tissue formation (“3-H concept”) as the major problem related to irradiated wounds.9 A new theory of irradiation tissue damage has been proposed on the basis of the radiation-induced fibroatrophic process to explain the damage to normal tissues, including bone and soft tissues, constituting the local and unavoidable sequelae of high-dose radiotherapy.10 According to this theory, there is a decrease in the soft tissue matrix, which is then replaced with fibrous tissue. Curi et al.11 recently published their histopathologic and histomorphometric analysis of irradiation injury in bone and the surrounding soft tissues of the jaw. The authors found seven histopathologic processes, including hyperemia, endarteritis, thrombosis, cell loss, hypovascularity, increase of fat in the bone marrow cavity, and fibrosis in irradiated specimens. Irradiation tissue injuries, such as hyperemia, endarteritis, and cell death, were found in the early period (up to 6 months) after radiotherapy, whereas other irradiation injuries, such as thrombosis, hypovascularization, and fibrosis, were identified as occurring at later times after radiotherapy.8 In the present case, the patient had been treated for SCC of the right retromolar trigone area with a combination of surgery and postoperative radiotherapy in high total dose (68 Gy) 8 years earlier. In light of the clinical presentation of tongue necrosis, we considered some conditions in our differential diagnosis, such as trauma, neoplasms, and, mainly, systemic vasculitis. Giant cell arteritis (Horton disease) is chronic vasculitis of large- and medium-sized vessels and commonly affects those over the age of 50 years. Clinical signs and symptoms are usually fever, claudication of the jaw, and temporal headache. Less common
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Fig. 4. A, Tongue wound healing 2 weeks after surgery demonstrating exposure of underlying ulcerated tissue. B, Tongue wound healing 1 month after glossectomy. C, Tongue complete wound healing 6 months after surgery demonstrating full epithelization.
signs and symptoms include dysphagia, cough, hearing loss, and necrosis of the tongue.1-7 Lingual necrosis is a known complication of giant cell arteritis, commonly affecting one side of the tongue.1-7 Bilateral necrosis has been described in a few cases, but it is considered extremely rare because of the rich lingual vascular supply.1-4 The American College of Rheumatology (ACR) has established classification criteria for the diagnosis of giant cell arteritis. According to the ACR, patients should present at least three out of five positive findings to meet the diagnosis criteria: (1) age older than 50 years at the onset of the disease; (2) new onset of localized headache; (3) abnormal temporal artery with tenderness or decreased pulse; (4) erythrocyte sedimentation rate higher than 50 mm/hr; and (5) biopsy of the artery showing necrotizing arteritis with predominant mononuclear cell infiltrate or granulomatous process with multinucleated giant cells.12 The ACR diagnostic tool does not include any lingual symptomatology among its criteria.12 Except age over 50 years at onset of disease, our patient did not meet three of the five ACR criteria required to make the diagnosis of giant cell arteritis. Radiation therapy causes injuries to bone and soft tissues, as well as immediate and late oral complications. Although the exact definition of ORN remains under discussion, more specifically regarding its timing and radiographic and histologic features, ORN has been defined as an irradiated bone that becomes devitalized and exposed through overlying mucosa, persisting without healing for a 2- to 3-month period in the
absence of tumor recurrence or metastasis.9,10,13,14 The onset of ORN may be related to any type of trauma or may occur spontaneously.15,16 Tooth extraction is the type of trauma most frequently related to the development of ORN.11,15-20 Tongue necrosis in association with ORN secondary to head and neck irradiation has not been reported in the literature. In the present case, there is a distinct possibility that the extractions and administration of local anesthesia with a vasoconstrictor contributed to the onset of ORN and that these two events together may have influenced the blood supply to the tongue. Radiation is the main etiologic factor in the development of bone and soft tissue necrosis and depends on the dose administered.15-20 It is known that wounds in irradiated tissues (bone and soft tissues) do not heal well, and risk factors for ORN include location in the posterior mandible, doses of radiation higher than 60 Gy, and the requirement of wound healing after surgical procedures (exodontia), which may be related to the present case.15-20 Treatment of tongue necrosis usually consists of surgical debridement and healing by secondary intention in cases of small areas of necrosis. Tongue resection (glossectomy) with primary closure has been indicated for large necrotic areas, and considerable deformity of the tongue should be expected in these cases.
CONCLUSIONS We presented a rare case of bilateral tongue necrosis occurring simultaneously with bilateral ORN of the jaw
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CASE REPORT Curi et al. e5
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secondary to head and neck irradiation. Although this is rare, the practitioner must be aware of the factors that instigate ORN; these factors may include use of an anesthetic with a vasoconstrictor and dental extractions involving the posterior mandible that has received greater than 60 Gy of radiation. The authors would like to thank Leila Felipini (Universidade do Sagrado Coração) for reviewing the English language of this manuscript.
REFERENCES 1. Zaragoza JR, Vernon N, Ghaffari G. Tongue necrosis as an initial manifestation of giant cell arteritis: case report and review of the literature. Case Rep Rheumatol. 2015;2015:901795. 2. Rockey JG, Anand R. Tongue necrosis secondary to temporal arteritis: a case report and literature review. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2002;94:471-473. 3. Zadik Y, Findler M, Maly A, Rushinek H, Czerninski R. A 78year-old woman with bilateral tongue necrosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:15-19. 4. Grant SW, Underhill HC, Atkin P. Giant cell arteritis affecting the tongue: a case report and review of the literature. Dent Update. 2013;40:673-674. 5. Gault DT. Tongue necrosis after radical neck dissection. Head Neck Surg. 1988;10:344-345. 6. Hemar P, Kennel P, Piller P, Herman D, Methlin A, Conraux C. Lingual necrosis after neck irradiation. Ann Otolaryngol Chir Cervicofac. 1993;110:351-354 [in French]. 7. David JM, Paty E, Bachaud JM, Vignaud JR. Lingual necrosis after radiotherapy. Radiation arteritis? Rev Stomatol Chir Maxillofac. 1989;90:334-336 [in French]. 8. M.D. Anderson cancer Center. Diseasedtongue cancer (2009) (Internet). The University of Texas M.D. Anderson Cancer Center [updated 2009]. Available at: http://www.mdanderson.org/ Departments/headandneck/display.cfm-52k. Accessed January 20, 2016. 9. Marx RE. Osteoradionecrosis: a new concept of its pathophysiology. J Oral Maxillofac Surg. 1983;41:283-288. 10. Delanian S, Lefaix JL. The radiation-induced fibroatrophic process: therapeutic perspective via the antioxidant pathway. Radiother Oncol. 2004;73:119-131.
11. Curi MM, Cardoso CL, de Lima HG, Kowalski LP, Martins MD. Histopathologic and histomorphometric analysis of irradiation injury in bone and the surrounding soft tissues of the jaws. J Oral Maxillofac Surg. 2016;74:190-199. 12. Arend WP, Michel BA, Bloch DA, et al. The American College of Rheumatology 1990 criteria for the classification of Takayasu arteritis. Arthritis Rheum. 1990;33:1129-1134. 13. Epstein JB, Wong FL, Stevenson-Moore P. Osteoradionecrosis: clinical experience and a proposal for classification. Int J Oral Maxillofac Surg. 1987;45:104-110. 14. Teng MS, Futran ND. Osteoradionecrosis of the mandible. Curr Opin Otolaryngol Head Neck Surg. 2005;13:217. 15. Morrish RB Jr, Chan E, Silverman S Jr, Meyer J, Fu KK, Greenspan D. Osteoradionecrosis in patients irradiated for head and neck carcinoma. Cancer. 1981;47:1980-1983. 16. Curi MM, Dib LL. Osteoradionecrosis of the jaws: a retrospective study of the background factors and treatment in 104 cases. J Oral Maxillofac Surg. 1997;55:540-544. 17. Nabil S, Samman N. Risk factors for osteoradionecrosis after head and neck radiation: a systematic review. Oral Surg Oral Med Oral Pathol Oral Radiol. 2012;113:54-69. 18. Monroe AT, Flesher-Bratt D, Morris CG, Peddada AV. Prospectively-collected, tooth-specific dosimetry correlated with adverse dental outcomes. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122:158-163. 19. De Felice F, Thomas C, Patel V, et al. Osteoradionecrosis following treatment for head and neck cancer and the effect of radiotherapy dosimetry: the Guy’s and St Thomas’ Head and Neck Cancer Unit experience. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;122:28-34. 20. Raguse JD, Hossamo J, Tinhofer I, et al. Patient and treatmentrelated risk factors for osteoradionecrosis of the jaw in patients with head and neck cancer. Oral Surg Oral Med Oral Pathol Oral Radiol. 2016;121:215-221.
Reprint requests: Camila Lopes Cardoso, DDS, MSc, PhD Department of Oral and Maxillofacial Surgery Universidade do Sagrado Coração Rua Irmã Arminda Bauru São Paulo Brazil [email protected]
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Delayed tongue necrosis simultaneous with bilateral osteoradionecrosis of the jaw secondary to head and neck irradiation Marcos Martins Curi, DDS, MSc, PhD,a,b Camila Lopes Cardoso, DDS, MSc, PhD,a,b Anthony Froy Condezo Benites, DDS,c and Patrícia Martins Bueno, DDSc We present a rare case of massive tongue necrosis occurring simultaneously with bilateral osteoradionecrosis (ORN) of the jaw in a patient with a history of treatment, including surgery and postoperative radiotherapy, for a retromolar trigone carcinoma 8 years earlier. There is a distinct possibility that the extractions and administration of local anesthesia with a vasoconstrictor contributed to the onset of ORN; together, these events may have influenced the blood supply to the tongue. A glossectomy was performed after hyperbaric oxygen therapy. One month after the surgical procedure, the patient responded satisfactorily to the treatment, showing significant improvement in speech and oral food intake, as well as significant decrease in lingual pain. Although the simultaneous occurrence of these oral complications is rare, the practitioner must be aware of the factors that instigate ORN and compromise vasculature as well as the clinical signs of tongue necrosis. Additionally, the possibility of tongue necrosis secondary to irradiation of the head and neck should be taken into consideration when an irradiated patient undergoes tooth extractions under local anesthesia with agents containing epinephrine. (Oral Surg Oral Med Oral Pathol Oral Radiol 2016;-:e1-e5)
Tongue necrosis is a rare oral complication associated with irradiation of the head and neck region. This condition may attributed to a wide range of causes, including malignant tumors, use of a vasoconstrictor, severe hemorrhage, embolism, abscess of the floor of the mouth, syphilis, giant cell arteritis, chemotherapy, and previous head and neck radiotherapy.1-5 The tongue has a rich vascular supply, consisting mainly of the bilateral lingual, pharyngeal, and facial arteries, in addition to collateral circulation. Generally, when tongue necrosis is observed, it commonly affects one side of the tongue, mainly the tip or the anterior half.1-5 The base of the tongue is never involved. Few cases of bilateral tongue necrosis have been reported in the literature.1-5 There are no reports of tongue necrosis occurring simultaneously with osteoradionecrosis (ORN) of the jaw. Primary tumors of the tongue are common, whereas metastatic tumors rarely occur at this site. Squamous cell carcinoma (SCC) is the most frequent primary malignant neoplasm occurring at this site.6 Treatment for tongue cancer usually involves surgery to remove the cancer.6 Chemotherapy, radiation therapy, and targeted drug therapy may also be recommended, a
Department of Oral and Maxillofacial Surgery, Universidade do Sagrado Coração, Bauru, São Paulo, Brazil. b Department of Oral Surgery, Hospital Santa Catarina, São Paulo, Brazil. c Department of Oral Surgery, Universidade Sagrado Coração, Bauru, São Paulo, Brazil. Received for publication Jul 13, 2016; returned for revision Oct 5, 2016; accepted for publication Oct 8, 2016. Ó 2016 Elsevier Inc. All rights reserved. 2212-4403/$ - see front matter http://dx.doi.org/10.1016/j.oooo.2016.10.010
depending on other factors, including the type and stage of cancer, possible side effects, and overall health of the patient. Radical neck dissection with ligation of the external carotid artery in patients receiving radiotherapy of the head and neck region has been reported as a cause of unilateral tongue necrosis.6 A search of texts published until 2016 and included in the MEDLINE database was conducted using specific terms: “lingual necrosis,” “lingual infarction,” “tongue necrosis,” “tongue infarction,” “giant cell arteritis and tongue necrosis,” “lingual ischemia,” and “head and neck radiotherapy and lingual necrosis.” Among the search results, we found only three cases of tongue necrosis occurring after head and neck radiotherapy.5-7 Therefore, the purpose of this report was to delineate a case of massive tongue necrosis occurring simultaneously with bilateral ORN of the jaw in a patient with a history of surgery and postoperative radiotherapy for SCC of retromolar trigone.
CASE REPORT A 56-year-old male was referred by his oncologist physician for dysphagia caused by a painful, swollen, and discolored tongue. The patient had a medical history of treatment for SCC (T2 N2 M0) of the right retromolar trigone area with a combination of surgery (tumor resection/modified radical neck dissection) and postoperative fractionated radiotherapy (5 fractions/week; 2.0 Gy/fraction; 34 sessions) 8 years earlier. To obtain more information about the surgery, we contacted the head and neck surgeon, who informed us that the patient had received right radical neck dissection (lymph nodes levels II to IV) without ligation of the external carotid artery. A total of 68 Gy had been applied to the oral cavity and
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Fig. 1. A and B, Brownish-black discoloration, edema, and tenderness involving the anterior third of the tongue bilaterally upon initial evaluation with movement limitation that compromised the patient’s speech and deglutition. 56 Gy to the entire chain of cervical nodes. The patient completed treatment for head and neck cancer and attended all follow-up appointments. He had remained disease-free since the end of his treatment in 2008. His medical history was negative for vasoconstrictor use, syphilis, cardiac arrest, or embolization. The patient was not taking any medication. An initial oral examination revealed edema, tenderness, and bilateral, brownish-black discoloration involving the anterior third of the tongue, with movement limitation that compromised his speech and deglutition. This tongue tissue area was necrotic, without bleeding, and sharply demarcated. The mucosa of the posterior two-thirds of the tongue had a normal appearance. In addition to this tongue alteration, bilateral exposure of necrotic bone of the body of the mandible was detected during oral examination (Figures 1A and 1B). The patient had a dental history of bilateral multiple exodontia (first and second right and left molars), which had been performed by his dentist 12 months earlier. According to the dentist, the reason for dental extractions was caries caused by radiation. The surgical procedure had been performed with the patient under local anesthesia (three cartridges, lidocaine 2% with epinephrine 1:100,000), and there were no complications. According to the dentist, the surgical wound did not heal adequately, and soft tissue breakdown and bilateral necrotic bone exposure occurred 20 days after the surgery. The patient denied symptoms of fever, arthralgia, neurologic alterations, weight loss, visual disturbances, jaw claudication, or temporal tenderness. Hematologic examination results were within normal parameters (white blood cells: 3.8 kU/L, hemoglobin: 14.4 g/dL, hematocrit: 42.8%, platelet: 250 kU/L). The erythrocyte sedimentation rate and cross-reactive protein were within normal limit (15 mm/hr and 2.5 mg/L, respectively). Panoramic radiograph demonstrated irregular diffuse osteolysis affecting alveolar bone on both sides of the mandible’s body and teeth alveoli with delayed remodeling (Figure 2). Because there was a strong diagnostic hypothesis of tongue necrosis as a consequence of prior radiotherapy for head and neck cancer, a tongue biopsy was performed. The specimen revealed soft tissue necrosis without signs of malignancy. In light of the diagnosis, Horton syndrome (temporal arteritis) was excluded because claudication of the legs, localized headache, abnormal temporal artery with tenderness, and decreased pulse were not present, and the erythrocyte sedimentation rate was not higher than 50 mm/hr. A carotid Doppler examination of the neck arteries yielded normal findings. The patient refused to undergo a superficial
Fig. 2. Panoramic radiograph demonstrating irregular diffuse osteolysis affecting the alveolar bone of the mandible bilaterally. temporal artery biopsy. With regard to the clinical and radiologic findings of the bilateral bone exposure in the mandible, we considered the hypothesis of ORN of the jaw. The patient’s initial management started with hyperbaric oxygen therapy (30 sessions: 20 sessions before surgery and 10 sessions after surgery; 2.4 ATA; 90-minute session in a monoplace chamber). Subsequently, a glossectomy was performed with the patient under general anesthesia, resulting in secondary wound healing (Figure 3). Bilateral marginal bone resections were performed to treat ORN on both sides of the mandible. Microscopic examination of the tongue specimen revealed fibrous proliferation with extensive areas of hyalinization associated with obliterated blood vessel lumen. Microscopic examination of the bone specimens revealed necrotic bone associated with a nonspecific chronic inflammatory process and the presence of colonies of filamentous bacteria. These investigations confirmed the diagnosis of tongue necrosis and ORN caused by radiation therapy for head and neck cancer. One month after the surgical procedure, the patient responded satisfactorily to treatment with significant improvement in speech and oral food intake and decreased lingual pain. The tongue lesion and ORN of the jaw healed completely over a 6-month follow-up period (Figures 4A-4C).
DISCUSSION Tongue necrosis is generally rare and may be associated with a wide range of pathologies. Differential diagnosis in tongue necrosis should include malignancies (carcinoma, sarcomas, lymphomas, metastatic tumors);
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Fig. 3. Necrotic specimen of the tongue.
medication use (chemotherapy and vasopressin); cardiovascular problems (cardiac arrest, embolisms, hemorrhage); infectious diseases (syphilis and tuberculosis); systemic vasculitis disorders (giant cell arteritis); and chemotherapy and head and neck radiotherapy.1-7 Therefore, careful history taking and physical examination to determine the association with the signs and symptoms of tongue necrosis are essential for accurate and early diagnosis. Despite the fact that the tongue is a well-vascularized anatomic site, there are reports of unilateral lingual necrosis that usually involves its anterior half. However, there are some cases of bilateral involvement reported in the literature.1-7 The current case presented bilateral tongue necrosis involving the anterior third of the tongue in a patient with a history of radiation therapy (8 years earlier) for SCC of the right retromolar trigone area and bilateral multiple exodontias performed using a local anesthetic containing a vasoconstrictor. The rarity of tongue necrosis caused by irradiation of the head and neck region is obvious, as indicated by the search conducted on this subject revealing only the three cases reported in the literature.5-7 The tongue is a common anatomic site of occurrence of malignant primary tumors and a less frequent site of involvement by metastatic tumors.8 The combination of surgery and postoperative radiotherapy is the standard treatment for SCC of the tongue in the advanced stage.8 Advanced tongue SCC (T3 and T4) often
CASE REPORT Curi et al. e3
requires neck dissection.8 Radical neck dissection with ligation of the external carotid artery in patients who had received postoperative radiotherapy to the head and neck has been reported as a possible cause of tongue necrosis.1-7 Postoperative radiotherapy usually includes the primary site and both sides of the neck, regardless of its indication being related to the primary tumor or metastases. Our patient had a medical history of surgery (tumor resection/modified radical neck dissection) and postoperative radiotherapy for oral cancer. In the literature, there is a scarcity of clinical studies on the evaluation of radiation tissue injury in humans. Although it is known that the higher the total doses used in the treatment of head and neck tumors, the greater the tissue adverse effects, there is still uncertainty about the pathophysiology of irradiated tissue injury. The basic pathophysiology of irradiation tissue injury is normal tissue cell death and sublethal normal tissue cell damage, leading to a wound-healing defect. Marx9 proposed the concept of hypovascular, hypocellular, and hypoxic tissue formation (“3-H concept”) as the major problem related to irradiated wounds.9 A new theory of irradiation tissue damage has been proposed on the basis of the radiation-induced fibroatrophic process to explain the damage to normal tissues, including bone and soft tissues, constituting the local and unavoidable sequelae of high-dose radiotherapy.10 According to this theory, there is a decrease in the soft tissue matrix, which is then replaced with fibrous tissue. Curi et al.11 recently published their histopathologic and histomorphometric analysis of irradiation injury in bone and the surrounding soft tissues of the jaw. The authors found seven histopathologic processes, including hyperemia, endarteritis, thrombosis, cell loss, hypovascularity, increase of fat in the bone marrow cavity, and fibrosis in irradiated specimens. Irradiation tissue injuries, such as hyperemia, endarteritis, and cell death, were found in the early period (up to 6 months) after radiotherapy, whereas other irradiation injuries, such as thrombosis, hypovascularization, and fibrosis, were identified as occurring at later times after radiotherapy.8 In the present case, the patient had been treated for SCC of the right retromolar trigone area with a combination of surgery and postoperative radiotherapy in high total dose (68 Gy) 8 years earlier. In light of the clinical presentation of tongue necrosis, we considered some conditions in our differential diagnosis, such as trauma, neoplasms, and, mainly, systemic vasculitis. Giant cell arteritis (Horton disease) is chronic vasculitis of large- and medium-sized vessels and commonly affects those over the age of 50 years. Clinical signs and symptoms are usually fever, claudication of the jaw, and temporal headache. Less common
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Fig. 4. A, Tongue wound healing 2 weeks after surgery demonstrating exposure of underlying ulcerated tissue. B, Tongue wound healing 1 month after glossectomy. C, Tongue complete wound healing 6 months after surgery demonstrating full epithelization.
signs and symptoms include dysphagia, cough, hearing loss, and necrosis of the tongue.1-7 Lingual necrosis is a known complication of giant cell arteritis, commonly affecting one side of the tongue.1-7 Bilateral necrosis has been described in a few cases, but it is considered extremely rare because of the rich lingual vascular supply.1-4 The American College of Rheumatology (ACR) has established classification criteria for the diagnosis of giant cell arteritis. According to the ACR, patients should present at least three out of five positive findings to meet the diagnosis criteria: (1) age older than 50 years at the onset of the disease; (2) new onset of localized headache; (3) abnormal temporal artery with tenderness or decreased pulse; (4) erythrocyte sedimentation rate higher than 50 mm/hr; and (5) biopsy of the artery showing necrotizing arteritis with predominant mononuclear cell infiltrate or granulomatous process with multinucleated giant cells.12 The ACR diagnostic tool does not include any lingual symptomatology among its criteria.12 Except age over 50 years at onset of disease, our patient did not meet three of the five ACR criteria required to make the diagnosis of giant cell arteritis. Radiation therapy causes injuries to bone and soft tissues, as well as immediate and late oral complications. Although the exact definition of ORN remains under discussion, more specifically regarding its timing and radiographic and histologic features, ORN has been defined as an irradiated bone that becomes devitalized and exposed through overlying mucosa, persisting without healing for a 2- to 3-month period in the
absence of tumor recurrence or metastasis.9,10,13,14 The onset of ORN may be related to any type of trauma or may occur spontaneously.15,16 Tooth extraction is the type of trauma most frequently related to the development of ORN.11,15-20 Tongue necrosis in association with ORN secondary to head and neck irradiation has not been reported in the literature. In the present case, there is a distinct possibility that the extractions and administration of local anesthesia with a vasoconstrictor contributed to the onset of ORN and that these two events together may have influenced the blood supply to the tongue. Radiation is the main etiologic factor in the development of bone and soft tissue necrosis and depends on the dose administered.15-20 It is known that wounds in irradiated tissues (bone and soft tissues) do not heal well, and risk factors for ORN include location in the posterior mandible, doses of radiation higher than 60 Gy, and the requirement of wound healing after surgical procedures (exodontia), which may be related to the present case.15-20 Treatment of tongue necrosis usually consists of surgical debridement and healing by secondary intention in cases of small areas of necrosis. Tongue resection (glossectomy) with primary closure has been indicated for large necrotic areas, and considerable deformity of the tongue should be expected in these cases.
CONCLUSIONS We presented a rare case of bilateral tongue necrosis occurring simultaneously with bilateral ORN of the jaw
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CASE REPORT Curi et al. e5
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secondary to head and neck irradiation. Although this is rare, the practitioner must be aware of the factors that instigate ORN; these factors may include use of an anesthetic with a vasoconstrictor and dental extractions involving the posterior mandible that has received greater than 60 Gy of radiation. The authors would like to thank Leila Felipini (Universidade do Sagrado Coração) for reviewing the English language of this manuscript.
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Reprint requests: Camila Lopes Cardoso, DDS, MSc, PhD Department of Oral and Maxillofacial Surgery Universidade do Sagrado Coração Rua Irmã Arminda Bauru São Paulo Brazil [email protected]