J Oral Mamllofac 49:1003-1006.
Surg
1991
Multiple
Nodules of the Lip, Cheeks, and Tongue
TOSHITAKA MUTO, DDS, PHD,* KENICHI SATO, DDS, PHD, MD,t AND GREGORY J. LUTCAVAGE, DDS$ Differential Diagnosis
Case Presentation A 75-year-old woman was referred to our hospital by her dentist on July 27, 1982 for investigation of multiple, small, and soft painless nodules on the lateral borders of the tongue. The patient had noticed these swellings about 1 year before. The number and size of nodules increased gradually, and they began to interfere with the fit of the lower denture. In addition, she complained of a sore and painful tongue beginning approximately 3 months prior to this visit. Physical examination revealed the patient to be anemic, which contributed to her pallor and ease of fatigue. She had a somewhat swollen hands and foots, with partial loss of sensation. Blood pressure was 140190 mm Hg. and she had a rapid but regular pulse of 1IO beats per minute. The remaining physical findings were normal for the patient’s age. Except for a mild anemia and a positive test for protein in urine. the routine blood chemistry and hematology values were within normal limits. There was no facial asymmetry or swellings of the salivary glands, or submandibular and cervical lymph nodes. Inspection of the oral cavity revealed a grossly enlarged tongue with multiple, small, yellowish or dark-red nodules on all surfaces except the dorsal surface (Fig I). On the mucosa of the lower lip, there were multiple small, soft, and yellowish nodules which appeared to be fused in some areas (Fig 1B). The mucosa of the upper lip and both cheeks were also noted to have similar nodules or hemorrhagic-appearing raised lesions (Fig 2). On palpation, these nodules were soft and nontender. The secretion of the salivary glands seemed to be normal.
Gregory
with a painful min B,2 can also be associated tongue, as can pernicious anemia and iron deficiency anemia. Xerostomia also can predispose to painful tongue. This finding can be associated with Sjogren’s syndrome, medications that reduce salivary flow. and certain endocrine disorders. An association between the connective tissue disorder amyloidosis and painful tongue has also been reported. Because of generalized macroglossia seen in this case, this, as well as the pain, needs to be consid-
ered in the differential diagnosis. Acromegaly, an endocrine disturbance resulting from hypersecretion of growth hormone in the adult, can cause prominent osseous and soft-tissue enlargement. The macroglossia in the acromegalic patient can result in the mandibular teeth being displaced facially. Lymphangioma can also cause macroglossia if the tumor is of sufficient size. The tongue is one of the most common intraoral sites for this congenital lesion. Similarly, diffuse neurofibroma can produce a generalized macroglossia. Amyloidosis, a generalized connective tissue disease process characterized by extracellular deposition of the fibrous protein amyloid, is also associated with a prominent macroglossia. In the dentulous patient, tongue enlargement may be so pronounced as to produce a scalloped effect along the lateral and anterior borders of the tongue secondary to impingement on the lingual surfaces of the teeth. The nodular growths within the oral cavity in this case also need to be considered in the diagnosis. Tumors of neural origin, with their propensity for tongue involvement. should be included. Consider-
sity, Japan. t Chief Professor. Department of Oral Surgery, School of Medicine, Chiba University, Japan. # Chairman, Department of Surgery. Wayne Memorial Hospital, Goldsboro, NC. Address correspondence and reprint requests to Dr Muto: Department of Oral and Maxillofacial Surgery, School of Dentistry, Higashi-Nippon-Gakuen University. Tobetsu-cho, Ishikari-gun. Hokkaido, Japan. Association
of Oral and Maxillofacial
DDS
A variety of different conditions can be associated with a painful tongue. Fungal organisms, particularly Candida, can cause symptoms described as a burning sensation, and also involve the buccal mucosa and the oropharynx. Deficiencies in vita-
* Associate Professor, Department of Oral and Maxillofacial Surgery. School of Dentistry. Higashi-Nippon-Gakuen Univer-
0 1991 American
J. Llctcavage*
Sur-
geons 0278-2391/9114909-0013$3.00/0
1003
1004
FIGURE 1. Views of tongue and lower lip. A, Tongue showing macroglossia and multiple nodules on the lateral borders. B, Oral surface of lower lip showing multiple, small, raised nodules, and the undersurface of the tongue showing irregular-shaped, soft, yellowish lesions.
ations are the granular cell tumor, schwannoma, neurofibroma, and mucosal neuroma. The granular cell tumor can occur at any age and involve multiple sites. Although the lips and buccal
MULTIPLE
NODULES
OF THE ORAL MUCOSA
mucosa can be affected, the tongue is the most common site.‘,2 However, granular cell tumors usually do not have such a generalized distribution as noted in this case. Schwannomas can also occur anywhere in the oral cavity, with the tongue being the most common area involved. However, this tumor is usually solitary. Neurofibroma can occur as solitary or multiple lesions within the oral cavity. When part of the neurofibromatosis syndrome, the disease is inherited as an autosomal dominant trait. Seventy percent of patients will show significant oral manifestations3 Mucosal neuromas, as part of multiple endocrine neoplasia syndrome III, can be multiple and have a distribution which is very similar to that found in this case. However, the condition usually occurs in a much younger patient population, ie, children and young adults. The diffuse distribution of the nodular lesions along the labial-buccal mucosa, the floor of the mouth, and the ventral, lateral, and anterior surfaces of the tongue is suggestive of a generalized systemic process. Amyloidosis can have this type of distribution, resulting in nodular lesions that are nonpainful. These masses are a result of direct deposition of amyloid within the connective tissues. An incidental finding on physical examination of this patient was upper and lower extremity swelling. This could represent a peripheral manifestation of congestive heart failure and altered cardiac function secondary to amyloid infiltration of the myocardium. This may also account for the resting sinus tachycardia. The partial loss of sensation noted in the hands could be consistent with bilateral carpal tunnel syndrome precipitated by amyloid infiltration of the flexor retinacula of the wrists.4 The baseline laboratory data showed mild anemia
1005
MUTO ET AL
in addition to a proteinuria. Anemia can be an initial finding in patients with amyloidosis and can also account for the fatigue which is frequently reported.4*5 Further studies consisting of both serum and protein electrophoresis and immunoelectrophoresis would be helpful to differentiate between immunoglobulin-related amyloid and multiple myeloma. A Bence-Jones protein determination would also be indicated to rule out multiple myeloma, although the heat test can give a falsenegative result in as high as 50% of patients with light chain multiple myeloma.6 Finally, a skeletal radiographic survey would be helpful in this case to detect the osteolytic lesions that can be seen in multiple myeloma. Based upon the analysis of the data made available, I believe that this case represents amyloidosis, possibly associated with multiple myeloma. SUBSEQUENT CLINICAL COURSE
Biopsy specimens were taken from the nodules of the lateral border of the tongue and the lower lip mucosa. Microscopic evaluation showed the tissue to be covered with stratified squamous epithelium, beneath which was an area of fibrous connective tissue containing a hyalinized, eosinophilic. acellular material interpreted as amyloid. Quite frequently the accumulations of amyloid were deposited close to the epithelium. Deposits of amyloid also could be seen around and within the walls of blood vessels (Fig 3). These specimens, viewed under polarized light, showed material consistent with amyloid when stained with Congo red. The amyloid showed greenish birefringence (Fig 4). The patient was referred to an internist of our hospital for further evaluation. An electrocardiogram showed a slight depression of the ST segment and a mild lowvoltage change of activity. Chest films showed a slightly enlarged cardiac silhouette. Abdominal ultrasonography confirmed a mild splenomegaly.
FIGURE 3. Photomicrograph showing infiltration of the underlying connective tissue by amyloid (hematoxylineosin stain, orig;inal magnification X100).
Discussion Amyloidosis is a relatively rare disease of unknown origin characterized by the deposition of a proteinaceous substance in many tissues and organs. About 120 years ago, Virchow mentioned a substance that stained with iodine similar to starch and he called this substance amyloid (“starchlike”).’ Because of the variable and unpredictable deposition of amyloid. there are no signs and symptoms that are pathognomonic. Various symptoms are seen depending on the site of amyloid deposition. For example, cardiomegaly and congestive heart failure due to deposition in the heart, diarrhea due to involvement of the intestines, and right-sided heart failure due to pulmonary lesions are often seen.* The recent classification of amyloidosis is based on the biochemistry of the amyloid fibrils. There are two main groups. Type A (secondary) amyloid is a fibrillar protein of unknown origin that is seen in prolonged inflammatory diseases, genetic disease, and syndromes such as familial Mediterranean fever. Type B (primary) amyloid is thought to be of immune origin and this type of amyloid is also commonly seen in patients with multiple myeloma.’ Cranin and Gross” in 1967, Kielts” in 1964, and Flick and Lawrence” in 1980 reported cases of amyloidosis secondary to multiple myeloma where the first oral symptoms were sore gingiva, inability to wear dentures, and mucosal changes. Primary amyloidosis usually involves tissues such as the skin, mucous membrane, heart, and gastrointestinal tract, whereas secondary amyloidosis usually affects parenchymatous organs such as the liver, spleen, kidney, and adrenals.13
1006
MULTIPLE
NODULES OF THE ORAL MUCOSA
FIGURE 4. Same specimen as shown in Figure 3 showing birefringency after Congo red stain using polarized light (original magnification X 100).
Oral manifestations have been reported in 39% of patients. l4 Oral amyloidosis often presents with various manifestations, such as multiple soft nodules15V’6; hemorrhagic-appearing, raised lesions17; raised white lesions’*; rubbery swellings with a normal overlying mucosa’; macroglossia with’**15 or without’8,‘9 multiple nodules on the lateral borders of the tongue or with prominent crenation.4*‘6*20 The macroglossia may cause problems with swallowing and speech.“,r9 The diagnosis of amyloidosis must be made by tissue biopsy and depends on the demonstration of amyloid deposits by means of staining paraffinembedded sections with alkaline Congo red and optical birefringence under polarized light. I3
6.
7. 8. 9. 10.
11.
12. 13. 14.
References
15.
1. Peterson LJ: Granular cell tumor. Oral Surg 37:728, 1974
16.
2. Miller AS, Leifer C, Chen S, et al: Oral granular cell tumors. Oral Surg 44~227, 1977
17.
3. Regezi JA, Sciubba JJ: Oral Pathology Clinical-Pathologic Correlations. Philadelphia, PA, Saunders, 1989
18.
4. Akin RK, Barton K, Walters PJ: Amyloidosis, macroglossia, and carpal tunnel syndrome associated with myeloma. J Oral Surg 33:690, 1975 5. Meyer I, Lytle JJ, Cella RJ, et al: Clinicopathological
con-
19. 20.
ference. Case 23, part 2. Amyloidosis of the tongue secondary to multiple myeloma. J Oral Surg 36:459, 1978 Wilson JD, Braunwald E, Isselbacher KJ, et al (eds): Harrison’s Principles of Internal Medicine (ed 12). New York, NY, McGraw-Hill, 1991 Virchow R: Ueber den Gang der Amyloiden Degeneration. Virchows Arch [A] 8: 140, 1855 van der Waal 1. Fehmers MCO, Kraal ER: Amyloidosis: Its significance in oral surgery. Oral Surg 36:469, 1973 Shafer WG, Hine MK, Levy BM: A Textbook of Oral Pathology (ed 4). Philadelphia, PA, Saunders, 1983, p 627 Cranin AM, Gross ER: Severe oral and perioral amyloidosis as primary complication of multiple myeloma. Oral Surg 23:153, 1967 Kielts TR: Amyloidosis of the buccal mucosa as diagnostic precusor in multiple myeloma: Report of a case. J Am Dent Assoc 69:701, 1964 Flick WG, Lawrence FR: Oral amyloidosis as initial symptom of multiple myeloma. Oral Surg 49: 18, 1980 Lever WF, Schaumburg-Lever G: Histopathology of the Skin ted 5). Philadelphia, PA, Lippincot, 1975, p 386 Kyle RA, Greipp PR: Amyloidosis (AL): clinical and laboratory features in 229 cases. Mayo Clin Proc 56:665, 1983 Kraut RA, Buhler JE, LaRue JR, et al: Amyloidosis associated with multiple myeloma. Oral Surg 43:63, 1977 Stanback JS, Peagler FD: Primary amyloidosis. Oral Med 26~774, 1968 Salisbury PJ, Jacoway JR: Oral amyloidosis: A late complication of multiple myeloma. Oral Surg 56:48, 1983 Hicks KA, Dicke WR: Amyloidosis: Report of a case presenting with macroglossia. Br J Plast Surg 26:274, 1973 Dendy RA. Davies JR, Gorst DW: A tongue resection in macroglossia due to primary amyloidosis. Br J Oral Maxillofac Surg 27:329, 1989 Plezia RA, Tse J, Venkatachalam H, et al: Primary amyloidosis: Report of a case. J Oral Maxillofac Surg 46:613, 1987
Surg
1991
Multiple
Nodules of the Lip, Cheeks, and Tongue
TOSHITAKA MUTO, DDS, PHD,* KENICHI SATO, DDS, PHD, MD,t AND GREGORY J. LUTCAVAGE, DDS$ Differential Diagnosis
Case Presentation A 75-year-old woman was referred to our hospital by her dentist on July 27, 1982 for investigation of multiple, small, and soft painless nodules on the lateral borders of the tongue. The patient had noticed these swellings about 1 year before. The number and size of nodules increased gradually, and they began to interfere with the fit of the lower denture. In addition, she complained of a sore and painful tongue beginning approximately 3 months prior to this visit. Physical examination revealed the patient to be anemic, which contributed to her pallor and ease of fatigue. She had a somewhat swollen hands and foots, with partial loss of sensation. Blood pressure was 140190 mm Hg. and she had a rapid but regular pulse of 1IO beats per minute. The remaining physical findings were normal for the patient’s age. Except for a mild anemia and a positive test for protein in urine. the routine blood chemistry and hematology values were within normal limits. There was no facial asymmetry or swellings of the salivary glands, or submandibular and cervical lymph nodes. Inspection of the oral cavity revealed a grossly enlarged tongue with multiple, small, yellowish or dark-red nodules on all surfaces except the dorsal surface (Fig I). On the mucosa of the lower lip, there were multiple small, soft, and yellowish nodules which appeared to be fused in some areas (Fig 1B). The mucosa of the upper lip and both cheeks were also noted to have similar nodules or hemorrhagic-appearing raised lesions (Fig 2). On palpation, these nodules were soft and nontender. The secretion of the salivary glands seemed to be normal.
Gregory
with a painful min B,2 can also be associated tongue, as can pernicious anemia and iron deficiency anemia. Xerostomia also can predispose to painful tongue. This finding can be associated with Sjogren’s syndrome, medications that reduce salivary flow. and certain endocrine disorders. An association between the connective tissue disorder amyloidosis and painful tongue has also been reported. Because of generalized macroglossia seen in this case, this, as well as the pain, needs to be consid-
ered in the differential diagnosis. Acromegaly, an endocrine disturbance resulting from hypersecretion of growth hormone in the adult, can cause prominent osseous and soft-tissue enlargement. The macroglossia in the acromegalic patient can result in the mandibular teeth being displaced facially. Lymphangioma can also cause macroglossia if the tumor is of sufficient size. The tongue is one of the most common intraoral sites for this congenital lesion. Similarly, diffuse neurofibroma can produce a generalized macroglossia. Amyloidosis, a generalized connective tissue disease process characterized by extracellular deposition of the fibrous protein amyloid, is also associated with a prominent macroglossia. In the dentulous patient, tongue enlargement may be so pronounced as to produce a scalloped effect along the lateral and anterior borders of the tongue secondary to impingement on the lingual surfaces of the teeth. The nodular growths within the oral cavity in this case also need to be considered in the diagnosis. Tumors of neural origin, with their propensity for tongue involvement. should be included. Consider-
sity, Japan. t Chief Professor. Department of Oral Surgery, School of Medicine, Chiba University, Japan. # Chairman, Department of Surgery. Wayne Memorial Hospital, Goldsboro, NC. Address correspondence and reprint requests to Dr Muto: Department of Oral and Maxillofacial Surgery, School of Dentistry, Higashi-Nippon-Gakuen University. Tobetsu-cho, Ishikari-gun. Hokkaido, Japan. Association
of Oral and Maxillofacial
DDS
A variety of different conditions can be associated with a painful tongue. Fungal organisms, particularly Candida, can cause symptoms described as a burning sensation, and also involve the buccal mucosa and the oropharynx. Deficiencies in vita-
* Associate Professor, Department of Oral and Maxillofacial Surgery. School of Dentistry. Higashi-Nippon-Gakuen Univer-
0 1991 American
J. Llctcavage*
Sur-
geons 0278-2391/9114909-0013$3.00/0
1003
1004
FIGURE 1. Views of tongue and lower lip. A, Tongue showing macroglossia and multiple nodules on the lateral borders. B, Oral surface of lower lip showing multiple, small, raised nodules, and the undersurface of the tongue showing irregular-shaped, soft, yellowish lesions.
ations are the granular cell tumor, schwannoma, neurofibroma, and mucosal neuroma. The granular cell tumor can occur at any age and involve multiple sites. Although the lips and buccal
MULTIPLE
NODULES
OF THE ORAL MUCOSA
mucosa can be affected, the tongue is the most common site.‘,2 However, granular cell tumors usually do not have such a generalized distribution as noted in this case. Schwannomas can also occur anywhere in the oral cavity, with the tongue being the most common area involved. However, this tumor is usually solitary. Neurofibroma can occur as solitary or multiple lesions within the oral cavity. When part of the neurofibromatosis syndrome, the disease is inherited as an autosomal dominant trait. Seventy percent of patients will show significant oral manifestations3 Mucosal neuromas, as part of multiple endocrine neoplasia syndrome III, can be multiple and have a distribution which is very similar to that found in this case. However, the condition usually occurs in a much younger patient population, ie, children and young adults. The diffuse distribution of the nodular lesions along the labial-buccal mucosa, the floor of the mouth, and the ventral, lateral, and anterior surfaces of the tongue is suggestive of a generalized systemic process. Amyloidosis can have this type of distribution, resulting in nodular lesions that are nonpainful. These masses are a result of direct deposition of amyloid within the connective tissues. An incidental finding on physical examination of this patient was upper and lower extremity swelling. This could represent a peripheral manifestation of congestive heart failure and altered cardiac function secondary to amyloid infiltration of the myocardium. This may also account for the resting sinus tachycardia. The partial loss of sensation noted in the hands could be consistent with bilateral carpal tunnel syndrome precipitated by amyloid infiltration of the flexor retinacula of the wrists.4 The baseline laboratory data showed mild anemia
1005
MUTO ET AL
in addition to a proteinuria. Anemia can be an initial finding in patients with amyloidosis and can also account for the fatigue which is frequently reported.4*5 Further studies consisting of both serum and protein electrophoresis and immunoelectrophoresis would be helpful to differentiate between immunoglobulin-related amyloid and multiple myeloma. A Bence-Jones protein determination would also be indicated to rule out multiple myeloma, although the heat test can give a falsenegative result in as high as 50% of patients with light chain multiple myeloma.6 Finally, a skeletal radiographic survey would be helpful in this case to detect the osteolytic lesions that can be seen in multiple myeloma. Based upon the analysis of the data made available, I believe that this case represents amyloidosis, possibly associated with multiple myeloma. SUBSEQUENT CLINICAL COURSE
Biopsy specimens were taken from the nodules of the lateral border of the tongue and the lower lip mucosa. Microscopic evaluation showed the tissue to be covered with stratified squamous epithelium, beneath which was an area of fibrous connective tissue containing a hyalinized, eosinophilic. acellular material interpreted as amyloid. Quite frequently the accumulations of amyloid were deposited close to the epithelium. Deposits of amyloid also could be seen around and within the walls of blood vessels (Fig 3). These specimens, viewed under polarized light, showed material consistent with amyloid when stained with Congo red. The amyloid showed greenish birefringence (Fig 4). The patient was referred to an internist of our hospital for further evaluation. An electrocardiogram showed a slight depression of the ST segment and a mild lowvoltage change of activity. Chest films showed a slightly enlarged cardiac silhouette. Abdominal ultrasonography confirmed a mild splenomegaly.
FIGURE 3. Photomicrograph showing infiltration of the underlying connective tissue by amyloid (hematoxylineosin stain, orig;inal magnification X100).
Discussion Amyloidosis is a relatively rare disease of unknown origin characterized by the deposition of a proteinaceous substance in many tissues and organs. About 120 years ago, Virchow mentioned a substance that stained with iodine similar to starch and he called this substance amyloid (“starchlike”).’ Because of the variable and unpredictable deposition of amyloid. there are no signs and symptoms that are pathognomonic. Various symptoms are seen depending on the site of amyloid deposition. For example, cardiomegaly and congestive heart failure due to deposition in the heart, diarrhea due to involvement of the intestines, and right-sided heart failure due to pulmonary lesions are often seen.* The recent classification of amyloidosis is based on the biochemistry of the amyloid fibrils. There are two main groups. Type A (secondary) amyloid is a fibrillar protein of unknown origin that is seen in prolonged inflammatory diseases, genetic disease, and syndromes such as familial Mediterranean fever. Type B (primary) amyloid is thought to be of immune origin and this type of amyloid is also commonly seen in patients with multiple myeloma.’ Cranin and Gross” in 1967, Kielts” in 1964, and Flick and Lawrence” in 1980 reported cases of amyloidosis secondary to multiple myeloma where the first oral symptoms were sore gingiva, inability to wear dentures, and mucosal changes. Primary amyloidosis usually involves tissues such as the skin, mucous membrane, heart, and gastrointestinal tract, whereas secondary amyloidosis usually affects parenchymatous organs such as the liver, spleen, kidney, and adrenals.13
1006
MULTIPLE
NODULES OF THE ORAL MUCOSA
FIGURE 4. Same specimen as shown in Figure 3 showing birefringency after Congo red stain using polarized light (original magnification X 100).
Oral manifestations have been reported in 39% of patients. l4 Oral amyloidosis often presents with various manifestations, such as multiple soft nodules15V’6; hemorrhagic-appearing, raised lesions17; raised white lesions’*; rubbery swellings with a normal overlying mucosa’; macroglossia with’**15 or without’8,‘9 multiple nodules on the lateral borders of the tongue or with prominent crenation.4*‘6*20 The macroglossia may cause problems with swallowing and speech.“,r9 The diagnosis of amyloidosis must be made by tissue biopsy and depends on the demonstration of amyloid deposits by means of staining paraffinembedded sections with alkaline Congo red and optical birefringence under polarized light. I3
6.
7. 8. 9. 10.
11.
12. 13. 14.
References
15.
1. Peterson LJ: Granular cell tumor. Oral Surg 37:728, 1974
16.
2. Miller AS, Leifer C, Chen S, et al: Oral granular cell tumors. Oral Surg 44~227, 1977
17.
3. Regezi JA, Sciubba JJ: Oral Pathology Clinical-Pathologic Correlations. Philadelphia, PA, Saunders, 1989
18.
4. Akin RK, Barton K, Walters PJ: Amyloidosis, macroglossia, and carpal tunnel syndrome associated with myeloma. J Oral Surg 33:690, 1975 5. Meyer I, Lytle JJ, Cella RJ, et al: Clinicopathological
con-
19. 20.
ference. Case 23, part 2. Amyloidosis of the tongue secondary to multiple myeloma. J Oral Surg 36:459, 1978 Wilson JD, Braunwald E, Isselbacher KJ, et al (eds): Harrison’s Principles of Internal Medicine (ed 12). New York, NY, McGraw-Hill, 1991 Virchow R: Ueber den Gang der Amyloiden Degeneration. Virchows Arch [A] 8: 140, 1855 van der Waal 1. Fehmers MCO, Kraal ER: Amyloidosis: Its significance in oral surgery. Oral Surg 36:469, 1973 Shafer WG, Hine MK, Levy BM: A Textbook of Oral Pathology (ed 4). Philadelphia, PA, Saunders, 1983, p 627 Cranin AM, Gross ER: Severe oral and perioral amyloidosis as primary complication of multiple myeloma. Oral Surg 23:153, 1967 Kielts TR: Amyloidosis of the buccal mucosa as diagnostic precusor in multiple myeloma: Report of a case. J Am Dent Assoc 69:701, 1964 Flick WG, Lawrence FR: Oral amyloidosis as initial symptom of multiple myeloma. Oral Surg 49: 18, 1980 Lever WF, Schaumburg-Lever G: Histopathology of the Skin ted 5). Philadelphia, PA, Lippincot, 1975, p 386 Kyle RA, Greipp PR: Amyloidosis (AL): clinical and laboratory features in 229 cases. Mayo Clin Proc 56:665, 1983 Kraut RA, Buhler JE, LaRue JR, et al: Amyloidosis associated with multiple myeloma. Oral Surg 43:63, 1977 Stanback JS, Peagler FD: Primary amyloidosis. Oral Med 26~774, 1968 Salisbury PJ, Jacoway JR: Oral amyloidosis: A late complication of multiple myeloma. Oral Surg 56:48, 1983 Hicks KA, Dicke WR: Amyloidosis: Report of a case presenting with macroglossia. Br J Plast Surg 26:274, 1973 Dendy RA. Davies JR, Gorst DW: A tongue resection in macroglossia due to primary amyloidosis. Br J Oral Maxillofac Surg 27:329, 1989 Plezia RA, Tse J, Venkatachalam H, et al: Primary amyloidosis: Report of a case. J Oral Maxillofac Surg 46:613, 1987
