Oral amyloidosis associated with multiple myeloma: A diagnostic tool
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《中华医药杂志》英文版
Oral amyloidosis associated with multiple myeloma: A diagnostic tool(pdf)
1 Departament of Dermatology and Radiotherapy, Botucatu Medical School - UNESP, SP Brazil
2 Department of Ophtalmology and Otorhinolaringology,Botucatu Medical School - UNESP, SP Brazil
3 Department of Pathology, Botucatu Medical School - UNESP, SP Brazil
Correspondence to Daniel Araki Ribeiro, DDS, PhD, Departamento de Patologia, Faculdade de Medicina de Botucatu - UNESP, Distrito de Rubio Jr s/n, Botucatu - SP 18618-000, Brazil
Tel:55-14-3882 8255,Fax:55-14-3815 2348,E-mail:araki@fmb.unesp.br
[Abstract] Amyloidosis is a disease in which normal tissue is replaced with insoluble amyloid fibrils. In this article, a 70-year-old man in bad health conditions presenting weakness, parestesia, and severe weight loss complained of an enlargement of the tongue and ulcerative lesion is reported. Microscopic examination of the hematoxylin and eosin (H.E.) and the Congo red staining confirmed the diagnosing of oral amyloidosis. In order to investigate any associated disease, further examinations were performed. Such findings were significant to support multiple myeloma. The approach be addressed to health care professionals, specially otorhinolaryngologists and dentists since oral amyloidosis can be an indicative for systemic diseases such as multiple myeloma.
[Key words] amyloidosis; tongue; multiple myeloma
INTRODUCTION
Amyloidosis is a disease in which normal tissue is replaced with insoluble amyloid fibrils [1~3]. The term amyloid, meaning starch or cellulose, was coined by Virchow in the mid- 19th century to describe abnormal extracellular material seen in the liver at autopsy. The disease can be categorized as a primary process or may occur secondary as a chronic disease. In this case, a genetically variant protein appears to be present (hereditary amyloidosis) or a defect in the metabolism of the precursor protein such as induced by tuberculosis, Crohn′s disease, arthritis, plasma cell discrasia as well as other connective disorders[5~7]. To date, the etiopathogenesis of amyloidosis is still matter for debate[8].
Multiple myeloma is a malignant disease caused by the proliferation of abnormal plasma cells[9]. Taking into consideration that amyloidosis can be associated with hematological disorders[10~12], in this article, we were able to report a case of multiple myeloma diagnosed by means of oral amyloidosis.
CASE REPORT
A 70-year-old man was admitted in the Clinics Hospital of the Botucatu Medical School suffering from weakness, fatigue, paresthesia of left hand and severe weight loss in the last six months (~20 kg). Also, the patient complained of an enlargement of the tongue and oral ulcerative lesion. Oral clinical examination revealed macroglossia, and an ulcerative area with white patches shaped mucosal hyperplasia approximately 4 cm in diameter on the left side of the lateral border of the tongue (Figure 1). The clinical diagnosis was squamous cell carcinoma. An incisional biopsy was performed under local anesthesia. Microscopic examination of the hematoxylin and eosin (H.E.) specimen suggested the presence of massive deposits of amyloid in the connective tissue (Figure 2). To confirm the diagnosis, the sample was stained with Congo red and examined under polarized light. On the basis of this specific dye, it was possible to observe an apple green staining consistent with amyloid protein, confirming, therefore, the diagnosis of oral amyloidosis. Herein,further examinations were performed in order to investigate any associated systemic disease. Abnormal findings were detected and they included diffuse osteopenia in skull bone as depicted by X-ray and the peak of urinary free monoclonal proteins. The patient was forwarded to a specialist in hematology, in which an incisional biopsy of medullar tissue was made. This was significant for the concurrent diagnosis of multiple myeloma (Figure 3). To date, the patient is being treated with multiple courses of chemotherapy with anti-neoplastic compounds.
Figure 1 Ulcerative lesion with white patches in the lateral border of the tongue Figure 2 Photomicrography showing oral mucosa and connective tissue containing amyloid deposits (H. E. stain, 10×magnification) Figure 3 High power magnification of medullar tissue compatible with multiple myeloma (H.E. stain, 100×magnification)
DISCUSSION
Amyloidosis corresponds a group of diseases that represent the extracellular deposition of fibrillar proteins in organs and tissues[1]. The pathogenesis of amyloidosis appears to be multifactorial as a result of the production of amyloid fibrils in the extracellular matrix. The symptoms are fatigue, paresthesia, edema, and weight loss with wide spectrum of tissue and organ involvement. However, the diagnosis usually is not made until signs and symptoms are linked to a particular organ[1]. The organs most commonly involved are the kidney and the heart, either alone or in combination[6]. This is rapidly fatal in the majority of cases.
A tissue biopsy is used to establish a definitive diagnosis. The use of Congo red staining is considered the gold standard for diagnosing since the dye displays an affinity for the abnormal protein[10]. Some authors have argued that approximately one-third out of all patients with amyloidosis has oral manifestations[5]. The most common complaints from patients with oral involvement are macroglossia, an enlargement of the tongue with tooth indentations along the lateral border, followed by mucosal pain that a denture often can aggravate[12]. Sometimes, oral amyloid deposits show ulceration and submucosal hemorrhage overlying the lesions. Gingiva, tongue, and minor salivary glands have all been reported as potential sites[2]. Amyloid deposits of the tongue as diffuse or nodular enlargement is up to 40% of cases and it is the most frequently reported oral manifestation in patients with multiple myeloma[8]. It affects usually older adults (~65 years of age) and slight male predilection is present.
It is important to stress that amyloid material may occur in other areas of the maxillofacial complex causing visual impairment and cosmetic deformity[13]. The treatment of choice for amyloidosis is conservative excision, although recurrent lesions may appear in some cases[14]. Moreover, occlusal adjustment,nutritional counselling and frequent recalls to monitor the macroglossia should also be considered to improve the follow-up[14].
Independent of its mode of presentation, amyloidosis can be debilitating and may decrease of the quality of a patients' life. The association between amyloidosis and multiple myeloma is well established. Neverthless, this article describes a case of oral amyloidosis that was discovered prior to diagnosis of multiple myeloma. Therefore, the approach be addressed to health care professionals, specially otorhinolaryngologists and dentists since oral amyloidosis can be an indicative for systemic diseases such as multiple myeloma[15].
REFERENCES
1. Falk RH, Comenzo RL, Skinner M. Medical progress: the systemic amyloidosis. N Engl J Med，1997，337: 898-909.
2. Stooper ET, Sollecito TP, Chen SY. Amyloid deposition in the oral cavity: A retrospective study and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod，2003，95: 674-680.
3. Touart DM, Sau P. Cutaneous deposition diseases. Part I. J Am Acad Dermatol，1998，39: 149-171.
4. Gertz MA, Lacy MQ, DispenzierI A. Amyloidosis. Hematol Oncol Clin North Am，1999，13: 1211-1233.
5. Koloktronis A, Chatzigiannis I, Paloukidou N. Oral involvement in a case of AA amyloidosis. Oral Dis， 2003，9: 269-272.
6. Van der Waal N, Henzen-Logmans S, Van der Kwast WA, Van der Waal I. Amyloidosis of the tongue: a clinical and postmortem study. J Oral Pathol，1984，13: 632-639.
7. Breathnach SM. Amyloid and amyloidosis. J Am Acad Dermatol，1988，18: 1-16.
8. Raubenheimer EJ, Dauth J, Pretoris FJ. Multiple myeloma and amyloidosis of the tongue. J Oral Pathol，1988，17: 554-559.
9. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol，1995，32: 45-59.
10. Pereira CM, Gasparetto PF, Correa ME, Vigorito AC, De Almeida OP. Primary oral and perioral amyloidosis associated with multiple myeloma. Gen Dent，2005，53: 340-341.
11. Reinish EI, Ravib M, Srolovitz H, Gornitsky M. Tongue, primary amyloidosis and multiple myeloma. Oral Surg Oral Med Oral Pathol，1994，77: 121-125.
12. Madani M, Harwick, RD, Chen SY, Miller AS. Amyloidosis of the oral cavity: report of five cases. Compendium，1991， 12: 336-342.
13. Bernardini FP, Schneider S, De Conciliis C, Devoto MH. Advanced Periocular, Facial, and Oral Amyloidosis. Ophthal Plast Reconstr Surg， 2005，21: 397-398.
14. Salisburg PL, Jacoway, LR. Oral amyloidosis: a late complication of multiple myeloma. Oral Surg Oral Med Oral Pathol，1983， 56: 48-50.
15. Ariyaratnam S, Sweet C, Duxbury J. Low grade multiple myeloma that presented as a labial swelling - a case report. Br Dent J， 2005， 8: 433-435.
(Editor Emilia)(Eliana Maria Minicucci1, )
1 Departament of Dermatology and Radiotherapy, Botucatu Medical School - UNESP, SP Brazil
2 Department of Ophtalmology and Otorhinolaringology,Botucatu Medical School - UNESP, SP Brazil
3 Department of Pathology, Botucatu Medical School - UNESP, SP Brazil
Correspondence to Daniel Araki Ribeiro, DDS, PhD, Departamento de Patologia, Faculdade de Medicina de Botucatu - UNESP, Distrito de Rubio Jr s/n, Botucatu - SP 18618-000, Brazil
Tel:55-14-3882 8255,Fax:55-14-3815 2348,E-mail:araki@fmb.unesp.br
[Abstract] Amyloidosis is a disease in which normal tissue is replaced with insoluble amyloid fibrils. In this article, a 70-year-old man in bad health conditions presenting weakness, parestesia, and severe weight loss complained of an enlargement of the tongue and ulcerative lesion is reported. Microscopic examination of the hematoxylin and eosin (H.E.) and the Congo red staining confirmed the diagnosing of oral amyloidosis. In order to investigate any associated disease, further examinations were performed. Such findings were significant to support multiple myeloma. The approach be addressed to health care professionals, specially otorhinolaryngologists and dentists since oral amyloidosis can be an indicative for systemic diseases such as multiple myeloma.
[Key words] amyloidosis; tongue; multiple myeloma
INTRODUCTION
Amyloidosis is a disease in which normal tissue is replaced with insoluble amyloid fibrils [1~3]. The term amyloid, meaning starch or cellulose, was coined by Virchow in the mid- 19th century to describe abnormal extracellular material seen in the liver at autopsy. The disease can be categorized as a primary process or may occur secondary as a chronic disease. In this case, a genetically variant protein appears to be present (hereditary amyloidosis) or a defect in the metabolism of the precursor protein such as induced by tuberculosis, Crohn′s disease, arthritis, plasma cell discrasia as well as other connective disorders[5~7]. To date, the etiopathogenesis of amyloidosis is still matter for debate[8].
Multiple myeloma is a malignant disease caused by the proliferation of abnormal plasma cells[9]. Taking into consideration that amyloidosis can be associated with hematological disorders[10~12], in this article, we were able to report a case of multiple myeloma diagnosed by means of oral amyloidosis.
CASE REPORT
A 70-year-old man was admitted in the Clinics Hospital of the Botucatu Medical School suffering from weakness, fatigue, paresthesia of left hand and severe weight loss in the last six months (~20 kg). Also, the patient complained of an enlargement of the tongue and oral ulcerative lesion. Oral clinical examination revealed macroglossia, and an ulcerative area with white patches shaped mucosal hyperplasia approximately 4 cm in diameter on the left side of the lateral border of the tongue (Figure 1). The clinical diagnosis was squamous cell carcinoma. An incisional biopsy was performed under local anesthesia. Microscopic examination of the hematoxylin and eosin (H.E.) specimen suggested the presence of massive deposits of amyloid in the connective tissue (Figure 2). To confirm the diagnosis, the sample was stained with Congo red and examined under polarized light. On the basis of this specific dye, it was possible to observe an apple green staining consistent with amyloid protein, confirming, therefore, the diagnosis of oral amyloidosis. Herein,further examinations were performed in order to investigate any associated systemic disease. Abnormal findings were detected and they included diffuse osteopenia in skull bone as depicted by X-ray and the peak of urinary free monoclonal proteins. The patient was forwarded to a specialist in hematology, in which an incisional biopsy of medullar tissue was made. This was significant for the concurrent diagnosis of multiple myeloma (Figure 3). To date, the patient is being treated with multiple courses of chemotherapy with anti-neoplastic compounds.
Figure 1 Ulcerative lesion with white patches in the lateral border of the tongue Figure 2 Photomicrography showing oral mucosa and connective tissue containing amyloid deposits (H. E. stain, 10×magnification) Figure 3 High power magnification of medullar tissue compatible with multiple myeloma (H.E. stain, 100×magnification)
DISCUSSION
Amyloidosis corresponds a group of diseases that represent the extracellular deposition of fibrillar proteins in organs and tissues[1]. The pathogenesis of amyloidosis appears to be multifactorial as a result of the production of amyloid fibrils in the extracellular matrix. The symptoms are fatigue, paresthesia, edema, and weight loss with wide spectrum of tissue and organ involvement. However, the diagnosis usually is not made until signs and symptoms are linked to a particular organ[1]. The organs most commonly involved are the kidney and the heart, either alone or in combination[6]. This is rapidly fatal in the majority of cases.
A tissue biopsy is used to establish a definitive diagnosis. The use of Congo red staining is considered the gold standard for diagnosing since the dye displays an affinity for the abnormal protein[10]. Some authors have argued that approximately one-third out of all patients with amyloidosis has oral manifestations[5]. The most common complaints from patients with oral involvement are macroglossia, an enlargement of the tongue with tooth indentations along the lateral border, followed by mucosal pain that a denture often can aggravate[12]. Sometimes, oral amyloid deposits show ulceration and submucosal hemorrhage overlying the lesions. Gingiva, tongue, and minor salivary glands have all been reported as potential sites[2]. Amyloid deposits of the tongue as diffuse or nodular enlargement is up to 40% of cases and it is the most frequently reported oral manifestation in patients with multiple myeloma[8]. It affects usually older adults (~65 years of age) and slight male predilection is present.
It is important to stress that amyloid material may occur in other areas of the maxillofacial complex causing visual impairment and cosmetic deformity[13]. The treatment of choice for amyloidosis is conservative excision, although recurrent lesions may appear in some cases[14]. Moreover, occlusal adjustment,nutritional counselling and frequent recalls to monitor the macroglossia should also be considered to improve the follow-up[14].
Independent of its mode of presentation, amyloidosis can be debilitating and may decrease of the quality of a patients' life. The association between amyloidosis and multiple myeloma is well established. Neverthless, this article describes a case of oral amyloidosis that was discovered prior to diagnosis of multiple myeloma. Therefore, the approach be addressed to health care professionals, specially otorhinolaryngologists and dentists since oral amyloidosis can be an indicative for systemic diseases such as multiple myeloma[15].
REFERENCES
1. Falk RH, Comenzo RL, Skinner M. Medical progress: the systemic amyloidosis. N Engl J Med，1997，337: 898-909.
2. Stooper ET, Sollecito TP, Chen SY. Amyloid deposition in the oral cavity: A retrospective study and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod，2003，95: 674-680.
3. Touart DM, Sau P. Cutaneous deposition diseases. Part I. J Am Acad Dermatol，1998，39: 149-171.
4. Gertz MA, Lacy MQ, DispenzierI A. Amyloidosis. Hematol Oncol Clin North Am，1999，13: 1211-1233.
5. Koloktronis A, Chatzigiannis I, Paloukidou N. Oral involvement in a case of AA amyloidosis. Oral Dis， 2003，9: 269-272.
6. Van der Waal N, Henzen-Logmans S, Van der Kwast WA, Van der Waal I. Amyloidosis of the tongue: a clinical and postmortem study. J Oral Pathol，1984，13: 632-639.
7. Breathnach SM. Amyloid and amyloidosis. J Am Acad Dermatol，1988，18: 1-16.
8. Raubenheimer EJ, Dauth J, Pretoris FJ. Multiple myeloma and amyloidosis of the tongue. J Oral Pathol，1988，17: 554-559.
9. Kyle RA, Gertz MA. Primary systemic amyloidosis: clinical and laboratory features in 474 cases. Semin Hematol，1995，32: 45-59.
10. Pereira CM, Gasparetto PF, Correa ME, Vigorito AC, De Almeida OP. Primary oral and perioral amyloidosis associated with multiple myeloma. Gen Dent，2005，53: 340-341.
11. Reinish EI, Ravib M, Srolovitz H, Gornitsky M. Tongue, primary amyloidosis and multiple myeloma. Oral Surg Oral Med Oral Pathol，1994，77: 121-125.
12. Madani M, Harwick, RD, Chen SY, Miller AS. Amyloidosis of the oral cavity: report of five cases. Compendium，1991， 12: 336-342.
13. Bernardini FP, Schneider S, De Conciliis C, Devoto MH. Advanced Periocular, Facial, and Oral Amyloidosis. Ophthal Plast Reconstr Surg， 2005，21: 397-398.
14. Salisburg PL, Jacoway, LR. Oral amyloidosis: a late complication of multiple myeloma. Oral Surg Oral Med Oral Pathol，1983， 56: 48-50.
15. Ariyaratnam S, Sweet C, Duxbury J. Low grade multiple myeloma that presented as a labial swelling - a case report. Br Dent J， 2005， 8: 433-435.
(Editor Emilia)(Eliana Maria Minicucci1, )