132
Multiple Myeloma A Case Report Jean-Claude Petit* and
of the Periodontium.
Ugo Ripamonti
the presenting features leading to a diagnosis of multiple myeloma in a 38-year-old male. Ulcération and bleeding from a rapidly growing retromolar myelomatous mass, multiple foci of alveolar bone destruction and cortical expansion together with multifocal skeletal destruction were the hallmarks of the neoplastic process. Radiotherapy and chemotherapy brought a substantial, but temporary, remission with improvement of the periodontal condition. A sudden exacerbation of the disease reactivated the previous lesions, new ones developed, and the patient died 22 months after the diagnosis was made. J Periodontol 1990;61:132-137. Multiple
periodontal lesions were
Key Words: Multiple myeloma/diagnosis; periodontal disease/diagnosis.
A large variety of systemic pathologic processes may affect the periodontal tissues. Neoplastic proliferations of plasma cells in the jaw bones and oral soft tissues are not uncommon, and a number of reports have been published.1-9 The lesions are frequently situated at the mandibular angle region and are characterized by osteolysis with or without localized enlargement of the overlying soft tissues.10"17 A review of the literature revealed that the periodontal involvement by myelomatous conditions, although possibly present at the time of diagnosis, has not been reported in detail. In this paper, we describe an instance of multiple myeloma with extensive periodontal lesions which led to the discovery of the systemic neoplastic condition. A retromolar tumor, composed of plasma cells, was the first clinical manifestation of the neoplasm.
CASE REPORT Early in November
1986, a 38-year-old black male visited hospital complaining of moderate gingival bleeding when eating. General examination was not contributory; head and neck examination did not reveal any palpable lymph nodes. Oral examination showed erythema migrans involving the dorsum of the tongue and a generalized chronic gingivitis. A panoramic radiograph revealed, posterior to the right mandibular second molar, an irregular, patternless, feebly our
radiolucent area which was attributed to traumatic extraction of the right mandibular third molar a year previously. In mid-December 1986, a second oral examination revealed a discrete enlargement of the right retromolar papilla. This enlargement, extending towards the buccal and palatophar-
'Dcpartment of Oral Medicine and Periodontology, Faculty of Dentistry, University of Durban-Westville, Dormerton, South Africa. fMRC/University of the Witwatersrand, Dental Research Institute, Johannesburg, South Africa.
yngeal folds, was oval, about 2.5 cm in the larger diameter, sessile, slightly lobulated, rubbery, and covered by a mucosa showing an aphthous-like ulcer about 8 mm in diameter. The lesion was asymptomatic. However, upon further
questioning, the patient admitted that for a few months he had been experiencing fatigue, pain in the shoulders, in the chest when coughing, and in the right thigh. At this stage, a provisional clinical diagnosis of pleomorphic adenoma
with mucosal ulcération was made, but tuberculous osteomyelitis of the mandible was not ruled out in view of the general malaise, fatigue, and chest pain. Squamous cell carcinoma, mucoepidermoid carcinoma, or metastatic tumor were also included in the differential diagnosis. An incisional biopsy was taken from the right retromolar papilla and bleeding was controlled by suturing. A week later, the tumor had enlarged considerably (Fig. 1A) and a second ulcer was noticed. The lesion was now diffusely erythematous, soft, and painful upon palpation. A discrete cortical expansion of the buccal plate of the alveolar process was evident between the maxillary left lateral incisor and canine (Fig. IB). A periapical radiographie status (Fig. 2) disclosed multiple round or oval radiolucencies, varying in size from 2 to 8 mm, with either a faint or a definite edge, mainly seen in the interdental septa and around the empty alveolus of the mandibular third molar where several radiolucent lesions seemed to have coalesced (Fig. 3). A new panoramic radiograph revealed a radiolucency in the head of the condyles. A lateral skull projection showed multiple "punched out" radiolucencies of various sizes with irregular outlines scattered in the calvaría (Fig. 4). The combined examination of the lateral and posterioranterior projections and panoramic radiograph revealed a possible involvement of the left maxillary antrum, the pterygoid plate, and the left frontal region. Subsequently, a
Volume 61 Number 2
PETIT, RIPAMONTI
133
Figure 2: Multifocal areas of alveolar bone destruction are seen in this periapical radiographie status (arrowed). The osteolytic lesion between the first and second mandibular premolars (arrowed) mimics alveolar bone loss as seen in Periodontitis (December 23, 1986).
radiographie
skeletal survey revealed focal osteolytic lesions in the clavicles, ribs, and pubis. On the basis of these new clinical and radiographie findings, a clinical diagnosis of multiple myeloma was made. This was confirmed shortly after by the histopathologic report, by then available. The histologie examination revealed
infiltrated by a dense cell population with most of the nuclei having an open chromatin pattern highly suggestive of neoplastic plasma cells, some of them showing a distinct eosinophilic cytoplasm. Many mitoses were seen (Fig. 5). Immunoperoxidase studies disclosed that the cell population was monoclonal in origin and produced kappa a mucosa
134
J Pcriodontol 1990
February
MULTIPLE MYELOMA OF THE PERIODONTIUM
Table 1: Laboratory Findings of the Patient at the Time of the Clinical Diagnosis, Hospital Admission, and Follow Up
f
Reference
Patient's Values CO
Laboratory Test
12/86
1/87
1/88
10/88
_
Ranges (males)
Plasma/serum Protein cellulose acetate
electrophoresis
Total protein (gm/1) Albumin (gm/1) Globulin (gm/1) Alpha 1 (gm/1)
Alpha 2 (gm/1)
/ Figure 3:
Detail
of the right retromolar area (December 23, 1986).
Beta (gm/1) Gamma (gm/1) Creatinine (|xmol/l) Urea (mmol/1) Uric acid (mmol/1) Total calcium (mmol/1) Urine Bence Jones protein
Dipstick test Sulphosalicyclic acid test Bradshaw test
Hematology WBC ( X 109/1) RBC ( 10l2/l) Hgb (g/dl) Hct (1/1)
MCV (fl) MCH (pg) MCHC (g/dl) Platelets (xl09/l) ESR (mm/hr,
44 44 4 11 7 22 130 296 6.5 12.2 0.52 0.52 3.19 3.70
neg. neg.
neg. neg.
neg.
neg.
6 4.86 11.1 0.345 71 22.8 32.2 149 121
5.5 4.52 10.1 0.330 72 22 31 281 130
72 42.4 29.6 2.5 8.2 5.8 13.1 90 3.1
3.3 4.75 11.7 0.376 79 24.7 31.3 272 19
83 48.1 34.9 2.8 8.9 7.3 15.9 110 6.7 0.43 2.19
3.2
4.61 11.8 0.376 81.6 26.2 32.2 254
32
60-80 38-48 20-32
1.1- 3,2 5,3-11,2 4.2-8,7 5.3-13,7 64-112 1.78-8.55 0.09-0.42 2.02-2.60
7.8±3 5.4 ±0.7 16±2 0.47±0.05 90±9 30±2 34±2 130-400 3-5
Westergren)
Figure 4. cies
Lateral skull projection
(December 23, 1986).
showing multiple calvarial radiolucen-
Figure 5. Dense infiltrate ofplasmacytoid cells. (H & E, original magnification 1000).
light chain Immunoglobulins.
evant initial biochemical and
Blood
Arrows indicate mitoses
was
taken and the rel-
hematological findings
are
listed in Table 1. The patient was immediately referred to the Department of Oncology and Radiotherapy for further examination and
treatment. A CT scan of the head and neck disclosed soft tissue involvement of the left maxillary antrum and con-
firmed the partial destruction of the left antrum, the pterygoid, and the left frontal region. Treatment consisted of radiation to the main areas of disease and intermittent courses of chemotherapy. Each course consisted of both etoposide 100 mg and cyclophosphamide 50 mg 10 per os weekly, and adriamycin 90 mg IV and vincristine sulphate 1.5 mg IV at 5 week intervals. The patient missed a course of chemotherapy in April 1987 since he had developed a right 6th nerve palsy. He completed a course of radiotherapy to the base of the skull in mid-April 1987 and resumed chemotherapy shortly afterwards. For about a year, the patient declined to visit our Department for oral assessment and treatment. However, in the mean time, he continued treatment by chemotherapy and radiotherapy. He was seen again only in January 1988. The clinical examination disclosed that the oral lesions had subsided. A moderate xerostomia had developed due to radiotherapy. The removal of an abundant plaque covering the dento-gingival area of most teeth revealed generalized cervical caries of enamel. A new radiographie periapical status taken in January 1988 showed that most of the previous alveolar radiolucencies had disappeared (Figs. 6A, 6B, 6C, and 6D). A radiograph of the left acromio-clavicular joint showed partial regeneration of the head of the clavicle. At that time, he agreed to follow
Volume 61 Number 2
PETIT, RIPAMONTI
135
6A
Figure area.
6. Details
of the second periapical radiographie status taken one year after diagnosis.
A. Note
regeneration of the alveolar bone in the retromolar
B, C, and D. Reestablishment of the lamina dura and of the interproximal bone (January 18, 1988).
plan which consisted of oral hygiene education and motivation, scaling and polishing, the prescription of a saliva substitute, and regular topical application of a fluoride gel to prevent further progress of the multiple incipient caries. During 1988, he regularly attended the Department of Oncology and Radiotherapy for radiation to painful areas of bone involvement, and for chemotherapy which latterly was melphalan and prednisolone, subsequently changed to ifosfamide and mesna. Periodontal maintenance was performed bimonthly until mid-August 1988. Within 2 weeks of the last visit, an examination revealed a sudden exacerbation of the neoplastic process. A large exophytic mass had developed at the previous site of the original intra-oral lesion, and fatigue and generalized bone and joint aches had become more pronounced. A panoramic radiograph showed further bone destruction at the our treatment
of the second right maxillary molar, and a proliferative lesion occupying and protruding from the floor of the right maxillary antrum (Fig. 7). Two large masses had also developed on both sides of the sternum in spite of chemotherapy. His condition deteriorated rapidly and he died on October 21, 1988.
apices
DISCUSSION Six types of plasma cell dyscrasias have been recognized on the basis of clinico-anatomie patterns.18 Among these, multiple myeloma (MM) is the most common and is characterized by a neoplastic proliferation of multifocal- tumorous masses widespread throughout the skeleton and occasionally by secondary soft tissue involvement. Although osteolytic lesions may affect virtually any bone, the
vertebrae, ribs, skull, pelvis, jaw bones, femura, clavicles,
J Periodontol 136
MULTIPLE MYELOMA OF THE PERIODONTIUM
Figure 7. Detail of the panoramic radiograph taken 20 months after diagnosis. Note a focal osteolytic lesion at the apices of the right maxillary second molar and tumorous growth within the right antrum (arrowed), (August 24, 1988). and scapulae are the most commonly involved.18 In over one fourth of the reported cases, the mandible is affected,19-21 usually in the posterior body, angle region, and ramus.20 Radiographs show multiple small well-defined radiolucencies without sclerotic borders and confluence of isolated lytic lesions occurs as bone destruction progresses. When present, the multiple punched-out defects in the skull are highly suggestive of MM. The uncontrolled plasma cell proliferation is responsible for a variety of pathognomonic biochemical and immunological alterations. In 60% to 80% of patients with MM, electrophoretic analysis shows abnormally high plasma levels of monoclonal homogeneous Immunoglobulins, or one of its constituent Polypeptide; i.e., light chains (L chains) in the urine (Bence Jones protein). The free L chains, synthesized along with complete Immunoglobulins, are either kappa or lambda, and, due to their small size, are rapidly excreted in the urine of 60% to 80% of all patients affected with MM.18 The multifocal osteolysis of the skeleton sustains the frequently severe hypercalcaemia responsible for neurologic manifestations.18 Although in this patient MM followed a classical course, of particular significance were the multifocal periodontal lesions which suggested the diagnosis, later confirmed by the histologie examination and the laboratory investigations. It is worth noting that the age of onset is rather unusual. Indeed, less than 2% of myeloma patients are affected before the age of 40 years. The plasma cell proliferation in the angle of the mandible caused a poorly-defined bony alteration which, in the first panoramic radiograph, was erroneously interpreted as a defective healing of the socket (chronic osteomyelitis) after extraction of the third molar. The neoplastic involvement of the retromolar region,
February 1990 which at the time of our first oral examination was characterized by a painless discrete soft tissue enlargement, was thus interpreted as a primary lesion and a provisional diagnosis of pleomorphic adenoma of the retromolar pad was made. However, owing to weakness and chest ache, other systemic conditions, including tuberculosis, were not ruled out. A dramatic plasma cell proliferation occurred after the biopsy. At the time of suture removal, changes in the tumorous lesions included ulcération, and hemorrhage and pain were present during mandibular function. These pronounced clinical changes prompted us to reevaluate the patient. The multiple osteolytic lesions localized in the alveolar processes cast a completely different light on the significance of the poorly demarcated lesion in the angle area, now better defined by the periapical radiographs. At this point, a systemic skeletal pathologic process was strongly suspected and the dull pain in the chest and shoulders was attributed to bony infiltrations. The radiographie examination of the skull and thorax suggested the diagnosis of MM, soon after confirmed by the histopathologic examination. Chemotherapy and radiotherapy caused a substantial remission of the neoplastic process. Remission together with regeneration attempts were also localized at the level of the periodontal lesions. However, in spite of chemotherapy and radiotherapy, the progression of the disease led to neoplastic proliferation in previously affected sites, the appearance of additional neoplastic foci and death.
Acknowledgments
The authors thank Dr. J. Hille, Department of Oral Pathology, University of the Western Cape, Tygerberg, for the histological investigations. They are also indebted to Professor P.E. Cleaton-Jones and Dr. G. Penfold for critical comments on the manuscript, and to Professor J.P. Jordaan, Department of Oncology and Radiotherapy, Addington Hospital, Durban, for making the patient's file available. REFERENCES 1. Sippel HW, Natiella JR, Greene GW. Multiple myeloma: Review and report of a case. J Oral Surg 1969; 27:808. 2. Wood GD. Myelomatosis: A case report. Brit Dent J 1975; 139:472. 3. Ramon Y, Oberman M, Horowitz I, et al. A large mandibular tumor with a distinct radiological "sun-ray effect" as the primary manifestation of multiple myeloma. / Oral Surg 1978; 36:52. 4. Jagger RG, Helkimo M, Carlsson GE. Multiple myeloma involving the temporomandibular joint: Report of case. J Oral Surg 1978; 36:557. 5. Halpern KL, Calhoun NR. Pathological fracture of mandibular condyloid process associated with multiple myeloma: Report of case. / Oral Surg 1978; 36:560. 6. Epstein JB, Voss NJS, Stevenson-Moore P. Maxillofacial manifestations of multiple myeloma: An unusual case and review of the literature. Oral Surg Oral Med Oral Path 1984; 57:267. 7. Urade M, Sugi M, Nishimura , et al. IgA-K type myeloma with severe postextraction bleeding. Int J Oral Surg 1985; 14:162. 8. Yaegaki K, Kameyama T, Takenaka M, et al. Myelomatosis (IgD, lambda) discovered by oral manifestation. IntJ Oral Surg 1985; 14:381. 9. Raubenheimer EJ, Dauth J, de Coning JP. Multiple myeloma pre-
Volume 61 Number 2
10. 11.
12. 13.
14. 15.
16.
senting with extensive oral and perioral amyloidosis. Oral Surg Oral Med Oral Path 1986; 61:492. Raubenheimer EJ, Dauth J, Jordaan JB, et al. Multiple myeloma presenting as a solitary expansile mandibular tumor. / Oral Med 1987; 42:109. Miller CD, Goltry RR, Shenasky JH. Multiple myeloma involving the mandible: Report of a case. Oral Surg Oral Med Oral Path 1969; 28:603. Shawkat AH, Phillips JD. Multiple myeloma: Report of a case. Oral Surg Oral Med Oral Path 1974; 37:969. Barr GS, Zweig , Itkin AB. Intraoral corroboration of systemic plasma-cell myeloma: Abbreviated case report. Oral Surg Oral Med Oral Path 1976; 42:22. Tabachnick TT, Levine . Multiple myeloma involving the jaws and oral soft tissues. J Oral Surg 1976; 34:931. Wright BA, Wysocki GP, Bannerjee D. Diagnostic use of immunoperoxidase techniques for plasma cell lesions of the jaws. Oral Surg Oral Med Oral Path 1981; 52:615. Senn JS, Stoneman DW, Cheng G, et al. Multiple myeloma with
PETIT, RIPAMONTI
17.
18. 19. 20. 21.
22.
of
137
initial presentation in the jaw: A clinical-pathologic discussion. J Oral Pathol 1985; 14:282. Ozaki M, Yamanaka H. An unusual case of Bence Jones myeloma with extremely low levels of monoclonal Immunoglobulin. Oral Surg Oral Med Oral Path 1986; 61:498. Robbins SL, Cotran RS, Kummar V. Pathologic Basis of Disease. 3rd ed. Philadelphia: W.B. Saunders, 1984:688-692. Eversole LR. Clinical Outline of Oral Pathology. 2nd ed. Philadelphia: Lea & Febiger, 1984:255. Cataldo E, Meyer I. Solitary and multiple plasma-cell tumors of the jaws and oral cavity. Oral Surg Oral Med Oral Path 1966;22:628. Staine EC, Gibilisco JA. Oral Roentgenographic Diagnosis. 4th ed. Philadelphia: W.B. Saunders, 1975:217-219. Goaz PW, White SC. Oral Radiology. St. Louis: The C.V. Mosby Co., 1982:511-513.
Send reprint requests to: Dr. J.-C. Petit, Faculty of Dentistry, University Durban-Westville, Private Bag X03, 4015 Dormerton, South Africa. Accepted for publication August 14, 1989.
Multiple Myeloma A Case Report Jean-Claude Petit* and
of the Periodontium.
Ugo Ripamonti
the presenting features leading to a diagnosis of multiple myeloma in a 38-year-old male. Ulcération and bleeding from a rapidly growing retromolar myelomatous mass, multiple foci of alveolar bone destruction and cortical expansion together with multifocal skeletal destruction were the hallmarks of the neoplastic process. Radiotherapy and chemotherapy brought a substantial, but temporary, remission with improvement of the periodontal condition. A sudden exacerbation of the disease reactivated the previous lesions, new ones developed, and the patient died 22 months after the diagnosis was made. J Periodontol 1990;61:132-137. Multiple
periodontal lesions were
Key Words: Multiple myeloma/diagnosis; periodontal disease/diagnosis.
A large variety of systemic pathologic processes may affect the periodontal tissues. Neoplastic proliferations of plasma cells in the jaw bones and oral soft tissues are not uncommon, and a number of reports have been published.1-9 The lesions are frequently situated at the mandibular angle region and are characterized by osteolysis with or without localized enlargement of the overlying soft tissues.10"17 A review of the literature revealed that the periodontal involvement by myelomatous conditions, although possibly present at the time of diagnosis, has not been reported in detail. In this paper, we describe an instance of multiple myeloma with extensive periodontal lesions which led to the discovery of the systemic neoplastic condition. A retromolar tumor, composed of plasma cells, was the first clinical manifestation of the neoplasm.
CASE REPORT Early in November
1986, a 38-year-old black male visited hospital complaining of moderate gingival bleeding when eating. General examination was not contributory; head and neck examination did not reveal any palpable lymph nodes. Oral examination showed erythema migrans involving the dorsum of the tongue and a generalized chronic gingivitis. A panoramic radiograph revealed, posterior to the right mandibular second molar, an irregular, patternless, feebly our
radiolucent area which was attributed to traumatic extraction of the right mandibular third molar a year previously. In mid-December 1986, a second oral examination revealed a discrete enlargement of the right retromolar papilla. This enlargement, extending towards the buccal and palatophar-
'Dcpartment of Oral Medicine and Periodontology, Faculty of Dentistry, University of Durban-Westville, Dormerton, South Africa. fMRC/University of the Witwatersrand, Dental Research Institute, Johannesburg, South Africa.
yngeal folds, was oval, about 2.5 cm in the larger diameter, sessile, slightly lobulated, rubbery, and covered by a mucosa showing an aphthous-like ulcer about 8 mm in diameter. The lesion was asymptomatic. However, upon further
questioning, the patient admitted that for a few months he had been experiencing fatigue, pain in the shoulders, in the chest when coughing, and in the right thigh. At this stage, a provisional clinical diagnosis of pleomorphic adenoma
with mucosal ulcération was made, but tuberculous osteomyelitis of the mandible was not ruled out in view of the general malaise, fatigue, and chest pain. Squamous cell carcinoma, mucoepidermoid carcinoma, or metastatic tumor were also included in the differential diagnosis. An incisional biopsy was taken from the right retromolar papilla and bleeding was controlled by suturing. A week later, the tumor had enlarged considerably (Fig. 1A) and a second ulcer was noticed. The lesion was now diffusely erythematous, soft, and painful upon palpation. A discrete cortical expansion of the buccal plate of the alveolar process was evident between the maxillary left lateral incisor and canine (Fig. IB). A periapical radiographie status (Fig. 2) disclosed multiple round or oval radiolucencies, varying in size from 2 to 8 mm, with either a faint or a definite edge, mainly seen in the interdental septa and around the empty alveolus of the mandibular third molar where several radiolucent lesions seemed to have coalesced (Fig. 3). A new panoramic radiograph revealed a radiolucency in the head of the condyles. A lateral skull projection showed multiple "punched out" radiolucencies of various sizes with irregular outlines scattered in the calvaría (Fig. 4). The combined examination of the lateral and posterioranterior projections and panoramic radiograph revealed a possible involvement of the left maxillary antrum, the pterygoid plate, and the left frontal region. Subsequently, a
Volume 61 Number 2
PETIT, RIPAMONTI
133
Figure 2: Multifocal areas of alveolar bone destruction are seen in this periapical radiographie status (arrowed). The osteolytic lesion between the first and second mandibular premolars (arrowed) mimics alveolar bone loss as seen in Periodontitis (December 23, 1986).
radiographie
skeletal survey revealed focal osteolytic lesions in the clavicles, ribs, and pubis. On the basis of these new clinical and radiographie findings, a clinical diagnosis of multiple myeloma was made. This was confirmed shortly after by the histopathologic report, by then available. The histologie examination revealed
infiltrated by a dense cell population with most of the nuclei having an open chromatin pattern highly suggestive of neoplastic plasma cells, some of them showing a distinct eosinophilic cytoplasm. Many mitoses were seen (Fig. 5). Immunoperoxidase studies disclosed that the cell population was monoclonal in origin and produced kappa a mucosa
134
J Pcriodontol 1990
February
MULTIPLE MYELOMA OF THE PERIODONTIUM
Table 1: Laboratory Findings of the Patient at the Time of the Clinical Diagnosis, Hospital Admission, and Follow Up
f
Reference
Patient's Values CO
Laboratory Test
12/86
1/87
1/88
10/88
_
Ranges (males)
Plasma/serum Protein cellulose acetate
electrophoresis
Total protein (gm/1) Albumin (gm/1) Globulin (gm/1) Alpha 1 (gm/1)
Alpha 2 (gm/1)
/ Figure 3:
Detail
of the right retromolar area (December 23, 1986).
Beta (gm/1) Gamma (gm/1) Creatinine (|xmol/l) Urea (mmol/1) Uric acid (mmol/1) Total calcium (mmol/1) Urine Bence Jones protein
Dipstick test Sulphosalicyclic acid test Bradshaw test
Hematology WBC ( X 109/1) RBC ( 10l2/l) Hgb (g/dl) Hct (1/1)
MCV (fl) MCH (pg) MCHC (g/dl) Platelets (xl09/l) ESR (mm/hr,
44 44 4 11 7 22 130 296 6.5 12.2 0.52 0.52 3.19 3.70
neg. neg.
neg. neg.
neg.
neg.
6 4.86 11.1 0.345 71 22.8 32.2 149 121
5.5 4.52 10.1 0.330 72 22 31 281 130
72 42.4 29.6 2.5 8.2 5.8 13.1 90 3.1
3.3 4.75 11.7 0.376 79 24.7 31.3 272 19
83 48.1 34.9 2.8 8.9 7.3 15.9 110 6.7 0.43 2.19
3.2
4.61 11.8 0.376 81.6 26.2 32.2 254
32
60-80 38-48 20-32
1.1- 3,2 5,3-11,2 4.2-8,7 5.3-13,7 64-112 1.78-8.55 0.09-0.42 2.02-2.60
7.8±3 5.4 ±0.7 16±2 0.47±0.05 90±9 30±2 34±2 130-400 3-5
Westergren)
Figure 4. cies
Lateral skull projection
(December 23, 1986).
showing multiple calvarial radiolucen-
Figure 5. Dense infiltrate ofplasmacytoid cells. (H & E, original magnification 1000).
light chain Immunoglobulins.
evant initial biochemical and
Blood
Arrows indicate mitoses
was
taken and the rel-
hematological findings
are
listed in Table 1. The patient was immediately referred to the Department of Oncology and Radiotherapy for further examination and
treatment. A CT scan of the head and neck disclosed soft tissue involvement of the left maxillary antrum and con-
firmed the partial destruction of the left antrum, the pterygoid, and the left frontal region. Treatment consisted of radiation to the main areas of disease and intermittent courses of chemotherapy. Each course consisted of both etoposide 100 mg and cyclophosphamide 50 mg 10 per os weekly, and adriamycin 90 mg IV and vincristine sulphate 1.5 mg IV at 5 week intervals. The patient missed a course of chemotherapy in April 1987 since he had developed a right 6th nerve palsy. He completed a course of radiotherapy to the base of the skull in mid-April 1987 and resumed chemotherapy shortly afterwards. For about a year, the patient declined to visit our Department for oral assessment and treatment. However, in the mean time, he continued treatment by chemotherapy and radiotherapy. He was seen again only in January 1988. The clinical examination disclosed that the oral lesions had subsided. A moderate xerostomia had developed due to radiotherapy. The removal of an abundant plaque covering the dento-gingival area of most teeth revealed generalized cervical caries of enamel. A new radiographie periapical status taken in January 1988 showed that most of the previous alveolar radiolucencies had disappeared (Figs. 6A, 6B, 6C, and 6D). A radiograph of the left acromio-clavicular joint showed partial regeneration of the head of the clavicle. At that time, he agreed to follow
Volume 61 Number 2
PETIT, RIPAMONTI
135
6A
Figure area.
6. Details
of the second periapical radiographie status taken one year after diagnosis.
A. Note
regeneration of the alveolar bone in the retromolar
B, C, and D. Reestablishment of the lamina dura and of the interproximal bone (January 18, 1988).
plan which consisted of oral hygiene education and motivation, scaling and polishing, the prescription of a saliva substitute, and regular topical application of a fluoride gel to prevent further progress of the multiple incipient caries. During 1988, he regularly attended the Department of Oncology and Radiotherapy for radiation to painful areas of bone involvement, and for chemotherapy which latterly was melphalan and prednisolone, subsequently changed to ifosfamide and mesna. Periodontal maintenance was performed bimonthly until mid-August 1988. Within 2 weeks of the last visit, an examination revealed a sudden exacerbation of the neoplastic process. A large exophytic mass had developed at the previous site of the original intra-oral lesion, and fatigue and generalized bone and joint aches had become more pronounced. A panoramic radiograph showed further bone destruction at the our treatment
of the second right maxillary molar, and a proliferative lesion occupying and protruding from the floor of the right maxillary antrum (Fig. 7). Two large masses had also developed on both sides of the sternum in spite of chemotherapy. His condition deteriorated rapidly and he died on October 21, 1988.
apices
DISCUSSION Six types of plasma cell dyscrasias have been recognized on the basis of clinico-anatomie patterns.18 Among these, multiple myeloma (MM) is the most common and is characterized by a neoplastic proliferation of multifocal- tumorous masses widespread throughout the skeleton and occasionally by secondary soft tissue involvement. Although osteolytic lesions may affect virtually any bone, the
vertebrae, ribs, skull, pelvis, jaw bones, femura, clavicles,
J Periodontol 136
MULTIPLE MYELOMA OF THE PERIODONTIUM
Figure 7. Detail of the panoramic radiograph taken 20 months after diagnosis. Note a focal osteolytic lesion at the apices of the right maxillary second molar and tumorous growth within the right antrum (arrowed), (August 24, 1988). and scapulae are the most commonly involved.18 In over one fourth of the reported cases, the mandible is affected,19-21 usually in the posterior body, angle region, and ramus.20 Radiographs show multiple small well-defined radiolucencies without sclerotic borders and confluence of isolated lytic lesions occurs as bone destruction progresses. When present, the multiple punched-out defects in the skull are highly suggestive of MM. The uncontrolled plasma cell proliferation is responsible for a variety of pathognomonic biochemical and immunological alterations. In 60% to 80% of patients with MM, electrophoretic analysis shows abnormally high plasma levels of monoclonal homogeneous Immunoglobulins, or one of its constituent Polypeptide; i.e., light chains (L chains) in the urine (Bence Jones protein). The free L chains, synthesized along with complete Immunoglobulins, are either kappa or lambda, and, due to their small size, are rapidly excreted in the urine of 60% to 80% of all patients affected with MM.18 The multifocal osteolysis of the skeleton sustains the frequently severe hypercalcaemia responsible for neurologic manifestations.18 Although in this patient MM followed a classical course, of particular significance were the multifocal periodontal lesions which suggested the diagnosis, later confirmed by the histologie examination and the laboratory investigations. It is worth noting that the age of onset is rather unusual. Indeed, less than 2% of myeloma patients are affected before the age of 40 years. The plasma cell proliferation in the angle of the mandible caused a poorly-defined bony alteration which, in the first panoramic radiograph, was erroneously interpreted as a defective healing of the socket (chronic osteomyelitis) after extraction of the third molar. The neoplastic involvement of the retromolar region,
February 1990 which at the time of our first oral examination was characterized by a painless discrete soft tissue enlargement, was thus interpreted as a primary lesion and a provisional diagnosis of pleomorphic adenoma of the retromolar pad was made. However, owing to weakness and chest ache, other systemic conditions, including tuberculosis, were not ruled out. A dramatic plasma cell proliferation occurred after the biopsy. At the time of suture removal, changes in the tumorous lesions included ulcération, and hemorrhage and pain were present during mandibular function. These pronounced clinical changes prompted us to reevaluate the patient. The multiple osteolytic lesions localized in the alveolar processes cast a completely different light on the significance of the poorly demarcated lesion in the angle area, now better defined by the periapical radiographs. At this point, a systemic skeletal pathologic process was strongly suspected and the dull pain in the chest and shoulders was attributed to bony infiltrations. The radiographie examination of the skull and thorax suggested the diagnosis of MM, soon after confirmed by the histopathologic examination. Chemotherapy and radiotherapy caused a substantial remission of the neoplastic process. Remission together with regeneration attempts were also localized at the level of the periodontal lesions. However, in spite of chemotherapy and radiotherapy, the progression of the disease led to neoplastic proliferation in previously affected sites, the appearance of additional neoplastic foci and death.
Acknowledgments
The authors thank Dr. J. Hille, Department of Oral Pathology, University of the Western Cape, Tygerberg, for the histological investigations. They are also indebted to Professor P.E. Cleaton-Jones and Dr. G. Penfold for critical comments on the manuscript, and to Professor J.P. Jordaan, Department of Oncology and Radiotherapy, Addington Hospital, Durban, for making the patient's file available. REFERENCES 1. Sippel HW, Natiella JR, Greene GW. Multiple myeloma: Review and report of a case. J Oral Surg 1969; 27:808. 2. Wood GD. Myelomatosis: A case report. Brit Dent J 1975; 139:472. 3. Ramon Y, Oberman M, Horowitz I, et al. A large mandibular tumor with a distinct radiological "sun-ray effect" as the primary manifestation of multiple myeloma. / Oral Surg 1978; 36:52. 4. Jagger RG, Helkimo M, Carlsson GE. Multiple myeloma involving the temporomandibular joint: Report of case. J Oral Surg 1978; 36:557. 5. Halpern KL, Calhoun NR. Pathological fracture of mandibular condyloid process associated with multiple myeloma: Report of case. / Oral Surg 1978; 36:560. 6. Epstein JB, Voss NJS, Stevenson-Moore P. Maxillofacial manifestations of multiple myeloma: An unusual case and review of the literature. Oral Surg Oral Med Oral Path 1984; 57:267. 7. Urade M, Sugi M, Nishimura , et al. IgA-K type myeloma with severe postextraction bleeding. Int J Oral Surg 1985; 14:162. 8. Yaegaki K, Kameyama T, Takenaka M, et al. Myelomatosis (IgD, lambda) discovered by oral manifestation. IntJ Oral Surg 1985; 14:381. 9. Raubenheimer EJ, Dauth J, de Coning JP. Multiple myeloma pre-
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Send reprint requests to: Dr. J.-C. Petit, Faculty of Dentistry, University Durban-Westville, Private Bag X03, 4015 Dormerton, South Africa. Accepted for publication August 14, 1989.
