Q U I N T E S S E N C E I N T E R N AT I O N A L
ORAL MEDICINE
Mahnaz Fatahzadeh
Metastatic papillary thyroid carcinoma to maxilla: A rare case Mahnaz Fatahzadeh, DMD, MSD1/Gayathri Subramanian, DMD, PHD2/Steven R. Singer, DDS3 Metastatic involvement of oral osseous and soft tissues constitutes nearly 1% of all oral malignancies. However, maxillary involvement is uncommon and this phenomenon is even less likely when the primary source is thyroid. A rare case of papillary thyroid carcinoma metastatic to maxillary right posterior
alveolar process and sinus in a 43-year-old woman is described and the spectrum of metastatic oral disease is reviewed. The importance of including metastasis in the differential diagnosis of jaw lesions is also emphasized. (Quintessence Int 2015;46:431–435; doi: 10.3290/j.qi.a33689)
Key words: metastatic, oral, papillary thyroid carcinoma
Metastatic disease comprises a small fraction (about 1%) of malignant oral conditions with significant clinical relevance.1-4 Oral dissemination of a known primary lesion can be debilitating, as it is often associated with poor prognosis and low quality of life.2,3,5,6 Metastatic oral disease may also be the first evidence of underlying malignancy elsewhere in the body.1,2,4,6-9 In a recent review of 673 cases of oral metastasis by Hirshberg et al,7 23% of lesions were the initial sign of an occult malignancy elsewhere in the body. Metastatic spread may occur via lymphatics or hematogenously9 and the source of oral metastasis varies with gender.8,10 While in females, oral metastases originate most often from cancer of the breast, reproductive organ, kidney, and colo-rectum, common sources of oral metastasis in males are lung, prostate, kidney and liver primaries.6-9 1
Professor of Oral Medicine, Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
2
Assistant Professor, Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
3
Professor, Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
Correspondence: Dr Mahnaz Fatahzadeh, Department of Diagnostic Sciences, D-855, Rutgers School of Dental Medicine, 110 Bergen Street, Newark, NJ 07103, USA. Email: [email protected]
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The observation that the majority of oral metastasis in males originate from lung primaries, the second most common malignancy after prostate, suggests that factors other than tumor frequency affect the likelihood of spread to the oral region.7 These may include the tumor’s biologic behavior, aggressiveness, and preference for specific oral sites as its metastatic target.7 This implies that certain tumors bypass spread to a proximal region in favor of colonizing a specific distant site.9 Although metastatic cancer could potentially involve both osseous and soft tissues of the cavity, spread to the jaw is twice as common, with a predilection for mandible.2,4,7,11 Osseous jaw metastasis has a female predilection, with breast as the most common primary source.11 In contrast, spread to the oral mucosa is prevalent in males, with lung as the most common primary source.11 The most frequently reported soft tissue site for oral metastasis is attached gingiva.7 In contrast to oral mucosal spread, jaw metastasis is more likely to remain unrecognized, particularly with early focal lesions.7,9,11 It has been postulated that chronic gingival inflammation may favor both deposition and progression of malignant cells.7 Thyroid cancer, the most common cancer of endocrine origin,8 accounts for up to 6% of metastatic malig-
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a
b Fig 1 Clinical photo illustrating right palatal swelling and emergence of an exophytic hemorrhagic mass from the palatal gingival sulcus of the maxillary right molars, and buccal displacement of the maxillary right second molar by the growing mass.
nancies in the oral region.11,12 Spread to oral cavity from a thyroid primary is more common in patients over 45 years old6,13 and has a female predilection,6 possibly attributable to more frequent occurrence of thyroid cancer among women.5,6,14 Osseous metastasis from thyroid source is frequently mulifocal and symptomatic.14 The present article reports a rare case of metastatic papillary thyroid carcinoma (PTC) manifesting as an expansile mass in the right maxillary posterior alveolar process and sinus of an adult female.
CASE REPORT A 43-year-old Hispanic woman presented for the evaluation of a hemorrhagic mass in the right maxilla noted 3 weeks prior to the visit. She reported a history of traumatic ulceration and bleeding during oral functions. The past medical history was significant for hypertension and stage II, well-differentiated papillary thyroid carcinoma, follicular variant, unsuccessfully treated with total thyroidectomy and radioactive iodine treatment. She had completed a course of palliative radiation for widespread metastasis to the left lung, scalp, right shoulder, and bilateral hips. Medications included hydrochlorothiazide, levothyroxine, and oxycodone. She stated that with the appearance of the oral mass, her physician had discontinued sorafenib, a che-
432
c
Figs 2a to 2c CBCT imaging of the oral mass at the initial presentation. (a) Panoramic projection illustrating soft tissue mass in the maxillary sinus, loss of lamina dura surrounding maxillary right first and second molars, as well as destruction of alveolus posterior to first molar. (b) Coronal projection illustrating effacement of the right palate and floor of the right maxillary sinus. (c) Axial projection illustrating destruction and expansion of the right posterior alveolus.
motherapeutic agent she was taking for the management of metastatic disease. Social history was noncontributory and she denied allergies. Extraoral exam was negative for lymphadenopathy. Intraorally, the patient was dentate with good oral hygiene. The right posterolateral palate appeared swollen and had a spongy consistency on palpation. Also, a well-circumscribed, firm, exophytic mass buccally displacing the maxillary right second molar and emerging from the palatal gingival sulcus of the maxillary right molars was visible in the tuberosity region (Fig 1). Cone beam computed tomography (CBCT) investigations revealed a mass of soft tissue density approximately 3 cm in greatest dimension in the right maxillary sinus, loss of lamina dura surrounding maxillary right first and second molars, destruction of the alveolus posterior to the maxillary right first molar, and effacement of the sinus floor in this area (Fig 2). The clinical and radiographic findings were consistent with an aggressive process. Considering the patient’s medical history, a metastatic disease secondary to thyroid carcinoma was a likely possibility. However, primary malignancies such as lymphoma, minor salivary gland tumor, and a tumor of mesenchymal origin were also considered in the differential diagnosis. In view of the recent discontinuation of chemotherapy, the patient’s complete blood counts and coag-
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Q U I N T E S S E N C E I N T E R N AT I O N A L Fatahzadeh et al
Fig 3 Histologic photomicrograph illustrating papillary and follicular structures lined by cuboidal to columnar cells with roundto-ovoid basophilic nuclei within the connective tissue. Necrosis, hemorrhage, and rare abnormal mitotic figures were also noted (hematoxylin-eosin, 400× magnification).
ulation profile were reviewed prior to the biopsy procedure and were found to be within normal limits. An incisional biopsy of the exophytic mass revealed multiple fragments of oral mucosa surfaced by stratified squamous epithelium. Within the connective tissue, papillary and follicular structures lined by 1 to 2 rows of cuboidal-to-columnar cells with round-to-ovoid basophilic nuclei were visible. Necrosis, hemorrhage, and rare abnormal mitotic figures were also noted (Fig 3). Microscopic findings were consistent with a metastatic adenocarcinoma. Immunohistochemically, the specimen was positive for thyroglobulin, further corroborating the histologic features consistent with a thyroid origin. Correlation of the history, clinical findings, imaging, and histopathology confirmed the maxillary jaw lesion to be metastatic in nature. Our findings were communicated to the attending oncologist and the patient was scheduled for radiotherapy to manage metastatic oral disease.
DISCUSSION The histologic subtype of thyroid cancer impacts the incidence and site of metastatic spread.6 PTC, the most common histologic variant, accounts for nearly 80% of all thyroid malignancies.14,15 It often manifests as an asymptomatic, indolent mass with favorable prognosis and minimal potential for distant metastasis.15 The
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minority (10% to 25%) of thyroid malignancies are of follicular type.8,10,16 Follicular thyroid carcinoma (FTC) often affects individuals over the age of 50,8,14 is more common in the setting of low iodine intake,14 and results in higher mortality than its papillary counterpart.14 Follicular cells of thyroid give rise to this type of thyroid cancer, which is often well-differentiated and to varying degrees resembles normal thyroid histology.2,8 Clinical features of FTC may mimic arteriovenous malformation, as this variant is highly vascular and often exhibits pulsation or bruit when auscultated.5,6,17 A common variant of PTC with intermediate clinical features between PTC and FTC as well as an overall favorable outcome similar to that of PTC is follicular variant of PTC (FV-PTC).18 Histologically, it presents with the follicular pattern arrangement of tumor cells but classic ground glass nuclear features of PTC.18 The likelihood of hematogenous spread for FV-PTC is higher than in pure PTC but less than in FTC.18 In contrast, metastasis to regional lymph nodes is more common in FV-PTC than in FTC but less common than in PTC.18 Osseous spread of malignancy in the absence of lymphadenopathy in the context of PTC may raise suspicion for FV-PTC.19 Table 1 summarizes the clinical features of papillary and follicular histologic variants of thyroid cancer. The present case fits the age and sex (woman in early forties) of patients with papillary thyroid carcinoma; however, it is rather unusual in its oral manifestation. Although many primary cancers do metastasize to the bone, the spread to the oral region is rare.1,6,8 More typical osseous sites for thyroid metastases include sternum, vertebrae, pelvis, and the ribs.1,6,13 In addition, metastatic cancer has a predilection for the molar-premolar region of mandible,6,11 and maxilla is a rare site of oral metastasis,3,6 representing the target site in less than 20% of all oral metastasis to the jaws.3 Osseous metastasis is even less likely when the primary source is thyroid and in particular with the pure PTC which tends to spread via lymphatics.6,8 Spread of malignancy to the maxilla in this patient’s presentation together with the absence of lymphadenopathy on presentation support the hematogenous route of metastasis which is consistent with the histopathologic diagnosis of her tumor, namely FV-PTC.
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Table 1
A summary of the clinical features of papillary and follicular variants of thyroid cancer1,6,8,14,15,16
Papillary thyroid carcinoma (PTC)
Follicular thyroid carcinoma (FTC)
Most common histologic variant (80%)
2nd most common histologic variant (10% to 20%)
Mean age of 40 years
Older age predilection (mean age of 50 years)
Indolent behavior
More aggressive behavior
More favorable prognosis
More likely to cause mortality
Lymphatogenous dissemination
Hematogenous spread
Common metastasis to regional lymph nodes
Rare metastasis to regional lymph nodes
Less frequent distant metastasis
More frequent distant spread. Higher incidence of spread to bones, lung, and oral cavity
More common in regions of western hemisphere with high iodine content of food
More common in regions with endemic goiter
Table 2
A summary of the necessary steps to verify a malignant jaw lesion is metastatic1,9
Criteria
Definition
Histologic confirmation
Primary tumor and jaw lesions are histologically identical as per special staining, electron microcopy, or other studies
Location of metastasis
Metastatic lesion in a site atypical for primary oral tumors
Direct extension of primary tumor
Exclusion of direct extension to jaw bones from a primary oral tumor
Genetic analysis
Identical cytogenetics in both primary and metastatic jaw tumor
The absence of separate reporting to cancer registries renders it difficult to estimate incidence of oral metastasis.4 The low incidence of metastatic disease in the jaws compared to rest of the skeleton may be because inclusion of the jaws in the screening skeletal surveys for metastasis is not routine.1,8 Despite the shared blood supply, the incidence of metastatic spread between the osseous and mucosal tissues of the jaws as well as maxilla and mandible is unequally distributed.11 The greater preponderance of metastasis in posterior mandible may be attributed to the higher content of hematopoietic tissue, sinusoidal vascular spaces with reduced blood which may promote tumor deposition.8,11 Metastatic jaw lesions may be asymptomatic3 or present with ill-defined symptoms.1 Most commonly reported clinical findings include facial swelling, epistaxis, nasal obstruction, pain or paresthesia in the affected region, tooth mobility, and pathologic fracture.1-11,16 In a study of 390 cases of jaw metastasis, 55 patients had teeth extracted at the site of metastasis with an average time of 2 months between the extrac-
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tion and metastasis diagnosis.11 Metastatic lesions of gingiva may initially mimic benign inflammatory entities such as pyogenic granuloma, peripheral giant cell granuloma, or epulis.7 In this patient, the maxillary right second molar was significantly displaced towards the buccal sulcus by the growing mass, although there was no evidence of tooth mobility. The patient noted the right maxillary swelling 3 weeks prior to presentation and reported a history of traumatic ulceration and bleeding during oral functions, but no pain or paresthesia. Metastatic disease affecting the mandible is a wellknown cause of numb chin syndrome or mental nerve neuropathy.2,8,9 Oral metastasis is frequently associated with simultaneous multifocal involvement of the body and, in particular, the skeletal structures.6 On presentation, the patient also had widespread metastasis to the left lung, scalp, right shoulder, and bilateral hips, for which she had completed a course of palliative radiation. The imaging techniques of choice for delineation of osseous malignancy is computed tomography (CT) scan, although plain x-ray, bone scintigraphy with tech-
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Q U I N T E S S E N C E I N T E R N AT I O N A L Fatahzadeh et al
netium 99mTc, and 131I whole body scan following total thyroidectomy may also be used.9,11,16 Metastatic lesions from a follicular or papillary thyroid source typically appear osteolytic with irregular, poorly-defined borders.1,2,6,11 Radiographic presentation of metastatic jaw lesions may resemble a pathologic fracture or an inflammatory condition such as periodontitis, periapical disease, or osteomyelitis, and delay the diagnosis.5,10,11 Interestingly, despite the presence of swelling and pain, osseous changes are not discernable by radiography in about 5% of metastatic jaw malignancies, prompting tissue sampling for definitive diagnosis.7,11 This may be due to the lack of contrast between the site of metastasis and the surrounding osseous tissues, which impacts the appreciation of radiologic changes.9 In order to establish that a jaw malignancy is metastatic in origin, correlation of medical history, clinical findings, imaging studies, and histopathologic features is necessary.1,6 Table 2 summarizes the criteria necessary for a malignant jaw lesion to be confirmed as metastatic. It is particularly important to differentiate primary intraoral malignancies from metastatic tumors which share similar microscopic features.7 Clinical history, histopathology, immunoperoxidase staining, and specific serum markers may help delineate the cellular origin of primary tumor.7 A number of factors affect the management strategy of choice for metastatic bone disease, which ranges from palliation to various combinations of surgery, radioactive iodine, radiotherapy, and chemotherapy.6,9 The first-line approach for metastatic lesions that concentrate iodine is radioactive iodine treatment (131I).16 Resection with or without external beam radiation may be considered for focal, solitary lesions that are not concentrating iodine.16 In contrast, inoperable or widespread disease is a candidate for palliation. Our patient received radiotherapy for the metastatic oral lesion, which had also been the approach for management for her skeletal metastasis.
CONCLUSION Metastatic oral disease is uncommon and may herald an occult malignancy elsewhere in the body. Definitive
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diagnosis of metastatic oral disease frequently requires an extensive work up, starting with a thorough medical history. Dental providers should be familiar with the spectrum of metastatic oral disease and include this possibility in the differential diagnosis of jaw lesions, particularly in patients with prior or current malignancy, and consider tissue sampling when warranted. High mortality rate and poor prognosis in patients with distant metastasis further highlights the importance of early detection for improved medical outcome.
REFERENCES 1. Narain S, Batra H. Metastatic carcinoma of maxilla secondary to primary follicular carcinoma of thyroid gland: a case report. Indian J Dent 2011;2(2):30–32. 2. Ismail SB, Abraham MT, Zaini ZB, et al. Metastatic follicular thyroid carcinoma to the mandible: a case report. Cases J 2009;2:6533. 3. Antunes AA, Antunes AP. Gnathic bone metastasis: a retrospective study of 10 cases. Braz J Otorhinolaryngol 2008;74:561–565. 4. Van der Waal RI, Buter J, van der Waal I. Oral metastases: report of 24 cases. Br J Oral Maxillofac Surg 2003;41:3–6. 5. Kahn MA, McCord PT. Metastatic thyroid carcinoma of the mandible: case report. J Oral Maxillofac Surg 1989;47:1314–1316. 6. Nikitakis NG, Polymeri A, Polymeris A, Sklavounou A. Metastatic papillary thyroid carcinoma to the maxilla: case report and literature review. Head Neck Pathol 2012;6:216–223. 7. Hirshberg A, Shnaiderman-Shapiro A, Kaplan I, Berger R. Metastatic tumors to the oral cavity: pathogenesis and analysis of 673 cases. Oral Oncol 2008;44:743–752. 8. Pasupula AP, Dorankula SP, Thokala MR, Kumar P. Metastatic follicular thyroid carcinoma to the mandible. Indian J Dent Res 2012;23:6:843. 9. Bodner L, Sion-Vardy N, Geffen DB, et al. Metastatic tumors to the jaws: a report of eight new cases. Med Oral Patol Oral Cir Bucal 2006;11:E132–E135. 10. Algahtani M, Alqudah M, Alshehri S, et al. Pathologic fracture of the mandible caused by metastatic follicular thyroid carcinoma. J Can Dent Assoc 2009;75:457–460. 11. Hirshberg A, Leibovich P, Buchner A. Metastatic tumors to the jawbones: analysis of 390 cases. J Oral Pathol Med 1994;23:337–341. 12. Clausen F, Poulsen H. Metastatic carcinoma to the jaws. Acta Pathol Microbiol Immunol Scand 1963;57:361–374. 13. Pittas AG, Adler M, Fazzari M, et al. Bone metastases from thyroid carcinoma: clinical characteristics and prognostic variables in one hundred forty-six patients. Thyroid 2000;10:261–268. 14. Grebe SK, Hay ID. Follicular thyroid cancer. Endocrinol Metab Clin North Am 1995;24:761–801. 15. Hodak SP, Burman KD. Thyroid carcinoma. Metastases to bone. In: Wartofsky L, VanNostrand D (eds). Thyroid Cancer: A comprehensive guide to clinical management. 2nd edition. Totowa: Humana Press, 2006:253–254, 517–518. 16. Krishnamurthy A, Vaidhyanathan A, Krishna KR. Metastasis of follicular thyroid carcinoma to the maxillary sinus. Indian J Nucl Med 2010;25:168–170. 17. Vural E, Hanna E. Metastatic follicular thyroid carcinoma to the mandible: a case report and review of the literature. Am J Otoralyngol 1998;19:198–202. 18. Yu XM, Schneider DF, Leverson G, Chen H, Sippel RS. Follicular variant of papillary thyroid carcinoma is a unique clinical entity: a population-based study of 10,740 cases. Thyroid 2013;23:1263–1268. 19. Bhansali A, Kataria RN, Subrahmanyam K, Radotra BD, Mathur SK. Maxillary mass as the presenting manifestation of papillary thyroid carcinoma. Indian J Cancer 2003;40:80–81.
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ORAL MEDICINE
Mahnaz Fatahzadeh
Metastatic papillary thyroid carcinoma to maxilla: A rare case Mahnaz Fatahzadeh, DMD, MSD1/Gayathri Subramanian, DMD, PHD2/Steven R. Singer, DDS3 Metastatic involvement of oral osseous and soft tissues constitutes nearly 1% of all oral malignancies. However, maxillary involvement is uncommon and this phenomenon is even less likely when the primary source is thyroid. A rare case of papillary thyroid carcinoma metastatic to maxillary right posterior
alveolar process and sinus in a 43-year-old woman is described and the spectrum of metastatic oral disease is reviewed. The importance of including metastasis in the differential diagnosis of jaw lesions is also emphasized. (Quintessence Int 2015;46:431–435; doi: 10.3290/j.qi.a33689)
Key words: metastatic, oral, papillary thyroid carcinoma
Metastatic disease comprises a small fraction (about 1%) of malignant oral conditions with significant clinical relevance.1-4 Oral dissemination of a known primary lesion can be debilitating, as it is often associated with poor prognosis and low quality of life.2,3,5,6 Metastatic oral disease may also be the first evidence of underlying malignancy elsewhere in the body.1,2,4,6-9 In a recent review of 673 cases of oral metastasis by Hirshberg et al,7 23% of lesions were the initial sign of an occult malignancy elsewhere in the body. Metastatic spread may occur via lymphatics or hematogenously9 and the source of oral metastasis varies with gender.8,10 While in females, oral metastases originate most often from cancer of the breast, reproductive organ, kidney, and colo-rectum, common sources of oral metastasis in males are lung, prostate, kidney and liver primaries.6-9 1
Professor of Oral Medicine, Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
2
Assistant Professor, Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
3
Professor, Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, USA.
Correspondence: Dr Mahnaz Fatahzadeh, Department of Diagnostic Sciences, D-855, Rutgers School of Dental Medicine, 110 Bergen Street, Newark, NJ 07103, USA. Email: [email protected]
VOLUME 46 • NUMBER 5 • MAY 2015
The observation that the majority of oral metastasis in males originate from lung primaries, the second most common malignancy after prostate, suggests that factors other than tumor frequency affect the likelihood of spread to the oral region.7 These may include the tumor’s biologic behavior, aggressiveness, and preference for specific oral sites as its metastatic target.7 This implies that certain tumors bypass spread to a proximal region in favor of colonizing a specific distant site.9 Although metastatic cancer could potentially involve both osseous and soft tissues of the cavity, spread to the jaw is twice as common, with a predilection for mandible.2,4,7,11 Osseous jaw metastasis has a female predilection, with breast as the most common primary source.11 In contrast, spread to the oral mucosa is prevalent in males, with lung as the most common primary source.11 The most frequently reported soft tissue site for oral metastasis is attached gingiva.7 In contrast to oral mucosal spread, jaw metastasis is more likely to remain unrecognized, particularly with early focal lesions.7,9,11 It has been postulated that chronic gingival inflammation may favor both deposition and progression of malignant cells.7 Thyroid cancer, the most common cancer of endocrine origin,8 accounts for up to 6% of metastatic malig-
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Q U I N T E S S E N C E I N T E R N AT I O N A L Fatahzadeh et al
a
b Fig 1 Clinical photo illustrating right palatal swelling and emergence of an exophytic hemorrhagic mass from the palatal gingival sulcus of the maxillary right molars, and buccal displacement of the maxillary right second molar by the growing mass.
nancies in the oral region.11,12 Spread to oral cavity from a thyroid primary is more common in patients over 45 years old6,13 and has a female predilection,6 possibly attributable to more frequent occurrence of thyroid cancer among women.5,6,14 Osseous metastasis from thyroid source is frequently mulifocal and symptomatic.14 The present article reports a rare case of metastatic papillary thyroid carcinoma (PTC) manifesting as an expansile mass in the right maxillary posterior alveolar process and sinus of an adult female.
CASE REPORT A 43-year-old Hispanic woman presented for the evaluation of a hemorrhagic mass in the right maxilla noted 3 weeks prior to the visit. She reported a history of traumatic ulceration and bleeding during oral functions. The past medical history was significant for hypertension and stage II, well-differentiated papillary thyroid carcinoma, follicular variant, unsuccessfully treated with total thyroidectomy and radioactive iodine treatment. She had completed a course of palliative radiation for widespread metastasis to the left lung, scalp, right shoulder, and bilateral hips. Medications included hydrochlorothiazide, levothyroxine, and oxycodone. She stated that with the appearance of the oral mass, her physician had discontinued sorafenib, a che-
432
c
Figs 2a to 2c CBCT imaging of the oral mass at the initial presentation. (a) Panoramic projection illustrating soft tissue mass in the maxillary sinus, loss of lamina dura surrounding maxillary right first and second molars, as well as destruction of alveolus posterior to first molar. (b) Coronal projection illustrating effacement of the right palate and floor of the right maxillary sinus. (c) Axial projection illustrating destruction and expansion of the right posterior alveolus.
motherapeutic agent she was taking for the management of metastatic disease. Social history was noncontributory and she denied allergies. Extraoral exam was negative for lymphadenopathy. Intraorally, the patient was dentate with good oral hygiene. The right posterolateral palate appeared swollen and had a spongy consistency on palpation. Also, a well-circumscribed, firm, exophytic mass buccally displacing the maxillary right second molar and emerging from the palatal gingival sulcus of the maxillary right molars was visible in the tuberosity region (Fig 1). Cone beam computed tomography (CBCT) investigations revealed a mass of soft tissue density approximately 3 cm in greatest dimension in the right maxillary sinus, loss of lamina dura surrounding maxillary right first and second molars, destruction of the alveolus posterior to the maxillary right first molar, and effacement of the sinus floor in this area (Fig 2). The clinical and radiographic findings were consistent with an aggressive process. Considering the patient’s medical history, a metastatic disease secondary to thyroid carcinoma was a likely possibility. However, primary malignancies such as lymphoma, minor salivary gland tumor, and a tumor of mesenchymal origin were also considered in the differential diagnosis. In view of the recent discontinuation of chemotherapy, the patient’s complete blood counts and coag-
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Q U I N T E S S E N C E I N T E R N AT I O N A L Fatahzadeh et al
Fig 3 Histologic photomicrograph illustrating papillary and follicular structures lined by cuboidal to columnar cells with roundto-ovoid basophilic nuclei within the connective tissue. Necrosis, hemorrhage, and rare abnormal mitotic figures were also noted (hematoxylin-eosin, 400× magnification).
ulation profile were reviewed prior to the biopsy procedure and were found to be within normal limits. An incisional biopsy of the exophytic mass revealed multiple fragments of oral mucosa surfaced by stratified squamous epithelium. Within the connective tissue, papillary and follicular structures lined by 1 to 2 rows of cuboidal-to-columnar cells with round-to-ovoid basophilic nuclei were visible. Necrosis, hemorrhage, and rare abnormal mitotic figures were also noted (Fig 3). Microscopic findings were consistent with a metastatic adenocarcinoma. Immunohistochemically, the specimen was positive for thyroglobulin, further corroborating the histologic features consistent with a thyroid origin. Correlation of the history, clinical findings, imaging, and histopathology confirmed the maxillary jaw lesion to be metastatic in nature. Our findings were communicated to the attending oncologist and the patient was scheduled for radiotherapy to manage metastatic oral disease.
DISCUSSION The histologic subtype of thyroid cancer impacts the incidence and site of metastatic spread.6 PTC, the most common histologic variant, accounts for nearly 80% of all thyroid malignancies.14,15 It often manifests as an asymptomatic, indolent mass with favorable prognosis and minimal potential for distant metastasis.15 The
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minority (10% to 25%) of thyroid malignancies are of follicular type.8,10,16 Follicular thyroid carcinoma (FTC) often affects individuals over the age of 50,8,14 is more common in the setting of low iodine intake,14 and results in higher mortality than its papillary counterpart.14 Follicular cells of thyroid give rise to this type of thyroid cancer, which is often well-differentiated and to varying degrees resembles normal thyroid histology.2,8 Clinical features of FTC may mimic arteriovenous malformation, as this variant is highly vascular and often exhibits pulsation or bruit when auscultated.5,6,17 A common variant of PTC with intermediate clinical features between PTC and FTC as well as an overall favorable outcome similar to that of PTC is follicular variant of PTC (FV-PTC).18 Histologically, it presents with the follicular pattern arrangement of tumor cells but classic ground glass nuclear features of PTC.18 The likelihood of hematogenous spread for FV-PTC is higher than in pure PTC but less than in FTC.18 In contrast, metastasis to regional lymph nodes is more common in FV-PTC than in FTC but less common than in PTC.18 Osseous spread of malignancy in the absence of lymphadenopathy in the context of PTC may raise suspicion for FV-PTC.19 Table 1 summarizes the clinical features of papillary and follicular histologic variants of thyroid cancer. The present case fits the age and sex (woman in early forties) of patients with papillary thyroid carcinoma; however, it is rather unusual in its oral manifestation. Although many primary cancers do metastasize to the bone, the spread to the oral region is rare.1,6,8 More typical osseous sites for thyroid metastases include sternum, vertebrae, pelvis, and the ribs.1,6,13 In addition, metastatic cancer has a predilection for the molar-premolar region of mandible,6,11 and maxilla is a rare site of oral metastasis,3,6 representing the target site in less than 20% of all oral metastasis to the jaws.3 Osseous metastasis is even less likely when the primary source is thyroid and in particular with the pure PTC which tends to spread via lymphatics.6,8 Spread of malignancy to the maxilla in this patient’s presentation together with the absence of lymphadenopathy on presentation support the hematogenous route of metastasis which is consistent with the histopathologic diagnosis of her tumor, namely FV-PTC.
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Table 1
A summary of the clinical features of papillary and follicular variants of thyroid cancer1,6,8,14,15,16
Papillary thyroid carcinoma (PTC)
Follicular thyroid carcinoma (FTC)
Most common histologic variant (80%)
2nd most common histologic variant (10% to 20%)
Mean age of 40 years
Older age predilection (mean age of 50 years)
Indolent behavior
More aggressive behavior
More favorable prognosis
More likely to cause mortality
Lymphatogenous dissemination
Hematogenous spread
Common metastasis to regional lymph nodes
Rare metastasis to regional lymph nodes
Less frequent distant metastasis
More frequent distant spread. Higher incidence of spread to bones, lung, and oral cavity
More common in regions of western hemisphere with high iodine content of food
More common in regions with endemic goiter
Table 2
A summary of the necessary steps to verify a malignant jaw lesion is metastatic1,9
Criteria
Definition
Histologic confirmation
Primary tumor and jaw lesions are histologically identical as per special staining, electron microcopy, or other studies
Location of metastasis
Metastatic lesion in a site atypical for primary oral tumors
Direct extension of primary tumor
Exclusion of direct extension to jaw bones from a primary oral tumor
Genetic analysis
Identical cytogenetics in both primary and metastatic jaw tumor
The absence of separate reporting to cancer registries renders it difficult to estimate incidence of oral metastasis.4 The low incidence of metastatic disease in the jaws compared to rest of the skeleton may be because inclusion of the jaws in the screening skeletal surveys for metastasis is not routine.1,8 Despite the shared blood supply, the incidence of metastatic spread between the osseous and mucosal tissues of the jaws as well as maxilla and mandible is unequally distributed.11 The greater preponderance of metastasis in posterior mandible may be attributed to the higher content of hematopoietic tissue, sinusoidal vascular spaces with reduced blood which may promote tumor deposition.8,11 Metastatic jaw lesions may be asymptomatic3 or present with ill-defined symptoms.1 Most commonly reported clinical findings include facial swelling, epistaxis, nasal obstruction, pain or paresthesia in the affected region, tooth mobility, and pathologic fracture.1-11,16 In a study of 390 cases of jaw metastasis, 55 patients had teeth extracted at the site of metastasis with an average time of 2 months between the extrac-
434
tion and metastasis diagnosis.11 Metastatic lesions of gingiva may initially mimic benign inflammatory entities such as pyogenic granuloma, peripheral giant cell granuloma, or epulis.7 In this patient, the maxillary right second molar was significantly displaced towards the buccal sulcus by the growing mass, although there was no evidence of tooth mobility. The patient noted the right maxillary swelling 3 weeks prior to presentation and reported a history of traumatic ulceration and bleeding during oral functions, but no pain or paresthesia. Metastatic disease affecting the mandible is a wellknown cause of numb chin syndrome or mental nerve neuropathy.2,8,9 Oral metastasis is frequently associated with simultaneous multifocal involvement of the body and, in particular, the skeletal structures.6 On presentation, the patient also had widespread metastasis to the left lung, scalp, right shoulder, and bilateral hips, for which she had completed a course of palliative radiation. The imaging techniques of choice for delineation of osseous malignancy is computed tomography (CT) scan, although plain x-ray, bone scintigraphy with tech-
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Q U I N T E S S E N C E I N T E R N AT I O N A L Fatahzadeh et al
netium 99mTc, and 131I whole body scan following total thyroidectomy may also be used.9,11,16 Metastatic lesions from a follicular or papillary thyroid source typically appear osteolytic with irregular, poorly-defined borders.1,2,6,11 Radiographic presentation of metastatic jaw lesions may resemble a pathologic fracture or an inflammatory condition such as periodontitis, periapical disease, or osteomyelitis, and delay the diagnosis.5,10,11 Interestingly, despite the presence of swelling and pain, osseous changes are not discernable by radiography in about 5% of metastatic jaw malignancies, prompting tissue sampling for definitive diagnosis.7,11 This may be due to the lack of contrast between the site of metastasis and the surrounding osseous tissues, which impacts the appreciation of radiologic changes.9 In order to establish that a jaw malignancy is metastatic in origin, correlation of medical history, clinical findings, imaging studies, and histopathologic features is necessary.1,6 Table 2 summarizes the criteria necessary for a malignant jaw lesion to be confirmed as metastatic. It is particularly important to differentiate primary intraoral malignancies from metastatic tumors which share similar microscopic features.7 Clinical history, histopathology, immunoperoxidase staining, and specific serum markers may help delineate the cellular origin of primary tumor.7 A number of factors affect the management strategy of choice for metastatic bone disease, which ranges from palliation to various combinations of surgery, radioactive iodine, radiotherapy, and chemotherapy.6,9 The first-line approach for metastatic lesions that concentrate iodine is radioactive iodine treatment (131I).16 Resection with or without external beam radiation may be considered for focal, solitary lesions that are not concentrating iodine.16 In contrast, inoperable or widespread disease is a candidate for palliation. Our patient received radiotherapy for the metastatic oral lesion, which had also been the approach for management for her skeletal metastasis.
CONCLUSION Metastatic oral disease is uncommon and may herald an occult malignancy elsewhere in the body. Definitive
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diagnosis of metastatic oral disease frequently requires an extensive work up, starting with a thorough medical history. Dental providers should be familiar with the spectrum of metastatic oral disease and include this possibility in the differential diagnosis of jaw lesions, particularly in patients with prior or current malignancy, and consider tissue sampling when warranted. High mortality rate and poor prognosis in patients with distant metastasis further highlights the importance of early detection for improved medical outcome.
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