CASE REPORTS

J Oral Maxillofac Surg

45~613-616. 1987

Primary Amyloidosis: Report of a Case

RICHARD A. PLEZIA, DDS, MS,* JACK TSE, DMD,t HEMA VENKATACHALAM, MD,* AND RICHARD K. WESLEY, DDS, MS5

Since Rokitansky and Virchow described signifi- cant observations of “waxy eosinophilic” tissue deposits in 1853, and subsequently designated them “amyloid” (starch-like), there have been tre- mendous advances in understanding of the disease process as well as the physical and biochemical na- ture of these tissue deposits. A major step in ad- vancing the research effort was unifying the defini- tion of amyloid as having, in all cases, a beta- pleated sheet structure’ that is normally not found in mammalian tissue in a pure conformation state.2

Over the years, clinicians have found that amy- loid deposition is not the consequence of a single- disease process, but rather it is precipitated by a variety of different processes. Amyloidosis is not only associated with recurrent and chronic infec- tion, but it is also related to a variety of lymphore- titular-derived dyscrasias and tumors of non-lym- phoreticular origin. It is also frequently associated with some pathology of aging such as senile and presenile dementia, and senile cardiomyopathy. The incidence of systemic amyloidosis was re- ported to be 0.6% to 0.7% in hospital populations.3

The oral manifestations of systemic amyloidosis are of special interest to oral surgeons and oral pa- thologists. It is not unusual for oral surgeons to be consulted by a physican to obtain a gingival or tongue biopsy for definitive histologic diagnosis. A knowledge of the pathogenesis and clinical presen- tation of this disease is, therefore, beneficial in clinical practice. Recently, we encountered a case of primary amyloidosis with significant oral mani-

* Oral and Maxillofacial Surgeon, Veterans Administration Medical Center, Allen Park, Michigan.

t Senior Resident, Oral and Maxillofacial Surgery Service, Sinai Hospital of Detroit. Detroit, Michigan.

$ Staff Pathologist, Director, Electron Microscopy, Veterans Administration Medical Center, Allen Park, Michigan.

I Chairman, Full Professor, Pathology Department, Univer- sity of Detroit Dental School, Detroit, Michigan.

Address correspondence and reprint requests to Dr. Plezia: Dental Service (160). Veterans Administration Medical Center, Southfield and Outer Drive, Allen Park, MI 48101.

0278-2391187 $0.00 + .25

festation. The purpose of this paper is to present the case and discuss the current knowledge on the clinical manifestation and therapy of the disease.

Report of a Case

A 54-year-old black man was first seen in the Oral and Maxillofacial Surgery Clinic in April 1984. His chief com- plaint was progressive enlargement of his tongue over the past month. His history revealed that he was well until approximately 10 months prior to the initial examination, when gradual onset of weakness and numbness of his upper extremities had developed. Bilateral carpal tunnel syndrome was diagnosed. The patient underwent medical and surgical therapy without significant relief. The symptoms of the right upper extremity weakness progres- sively increased. In February 1984, electromyographic studies of the right upper extremity demonstrated dener- vation activity of C5-C6.

Approximately seven months prior to this examina- tion, the patient developed visual disturbances. Examina- tion by a neuro-ophthalmologist revealed obvious clinical signs of left optic neuropathy. Visual studies were consis- tent with bilateral involvement. One month prior to ad- mission, the patient developed enlargement of his tongue, with a burning sensation, causing significant dysphagia. A biopsy of the tongue was performed in a private oral surgery office. A review of systems was significant for weight loss over the past 10 months, more over the past one month, for a total of 6.75 kg, and impotence over the past seven months.

The past medical history included arthroscopy and urethrocystoscopy with prostate biopsy in June 1983: laminectomy in 1967; hypertension that has been con- trolled with lopressor and dyazide; and gastritis that was treated with antacid. The familial history was negative for amyloidosis.

The patient was admitted to the hospital in April 1984 for further evaluation. Significant physical findings on admission examination included left optic atrophy on fundus examination and decreased visual acuity of left eye; oral examination revealed a firm and enlarged tongue, with decreased mobility, and indentation of the dentition on the lateral borders (Fig. 1); multiple small (l-2 mm diameter) firm nodules were found on the lower labial mucosa; bilateral firm, movable submandibular lymph nodes, approximately 5- 10 mm in diameter, were palpable in the neck; and neurologic examination re- vealed symmetrically decreased grip strength; decreased right bicep and deltoid strength; decreased left tricep strength; and decreased pinprick sensory function of the right lateral arm. The admission laboratory findings in-

613

614 PRIMARY AMYLOIDOSIS

in our clinic, and has shown only minimal oral change 2.5 years after the original diagnosis.

Discussion

FIGURE 1. Intraoral view showing a firm, enlarged, scal-

loped tongue.

eluded an elevated lymphocyte count and sedimentation rate: normal electrolytes; normal BUN and creatinine. and a total protein of 5.5 g (dGcreased). The chest ra- diograph was within normal limits, and the EKG showed no conductance disturbance.

The tongue biopsy was diagnosed as amyloidosis. A biopsy of lower labial mucosa was repeated for diagnostic confirmation and a workup to rule out multiple myeloma and other secondary causes was carried out. Serum im- munoglobin electrophoresis produced a normal profile and urine immunoglobulin electrophoresis was negative for Bence-Jones protein. Rheumatoid factor and antinu- clear antibody determinations were also negative, as was the PPD skin test to rule out tuberculosis. A total body scan with Tc-99m methylene diphosphate showed mild irregular, diffuse, nondiagnostic activity in the skull and increased activity in the lower lumbar spine and right knee joint compatible with postsurgical changes. The skull radiograph was non-diagnostic due to retention of dye from a previous myelogram.

The second biopsy of the lower labia1 mucosa viewed under polarized light revealed material consistent with amyloid when stained with Congo red (Fig. 2). Electron microscopic studies showed amyloid fibrils with a diam- eter of 110 to 180 nm (Fig. 3). The amyloid material ex- tracted from the lower lip biopsy retained its affinity for congo red and typical polarization characteristics when treated with potassium permanganate. The biopsy of ab- dominal skin, that was recommended by the dermatology service to rule out cutaneous involvement, was negative for amyloidosis.

The hematology service was consulted regarding a bone biopsy and an aspiration biopsy of bone marrow was obtained from the ileum. No amyloid material was seen in the biopsy. Binucleated and trinucleated plasma cells with opened nuclear chromatin were seen occasion- ally. The cytochemistry of the plasma cell aggregates in the aspirate showed monoclonal kappa light chains of im- munoglobulins. These findings, together with a plasma cell concentration of 2-4%, suggested a plasma cell dyscrasia. The final diagnosis was primary systemic amy- loidosis with gastrointestinal (macroglossia) and neuro- logical involvement. The patient was referred to the Mayo Clinic for treatment. The patient has been followed

This case of primary amyloidosis illustrates the diverse clinical presentations of the disease. Amy- loid deposition can effect virtually every tissue of the body. Although renal involvement is more common, the major cause of death in this disease is cardiac failure.4 Cardiac involvement with amyloid results in congestive heart failure or dysrhythmias due to deposits infiltrating the heart muscle and conduction fibers. Orthostatic hypotension or hy- pertension can also occur if amyloid deposits in- volve the autonomic nervous system. Other common autonomic dysfunctions are light-headed- ness or syncope, bladder dysfunction, and impo- tence in men. Peripheral neuropathy is usually distal, symmetric and progressive. Nephrotic syn- drome, with proteinuria, is the result of amyloid de- position along the basement membrane.

Macroglossia can be one of the most prominent manifestations of gastrointestinal involvement, and frequently it is the chief complaint that causes the patient to seek help. Other significant abdominal manifestations of amyloidosis include hepato- megaly, with elevation of liver enzymes. and mal- absorption with weight loss. Anemia and thrombo- cytosis may be major hematologic manifestations of the disease. Bleeding from deficiencies in various factors could be a major problem in management of these patients. Amyloidosis may also involve para- articular structures and resemble rheumatoid ar- thritis. A case of amyloid involvement of the tem- poromandibular joint has been reported.S Table 1 summarizes the major organ involvement of sys- temic amyloidosis.

The diagnosis of amyloidosis depends on the demonstration of amyloid deposits in tissue by means of either appropriate staining procedures and optical birefringence under polarized light, or electron microscopy.6 The tissue for biopsy can be obtained from the gingiva, tongue or rectal mucosa. To be adequate, the biopsy specimen must contain submucosa since amyloid deposits frequently in- volve more than the mucosa.

The diagnosis of primary amyloidosis cannot be made without exclusion of secondary amyloidosis due to chronic inflammatory conditions such as tu- berculosis, chronic osteomyelitis and rheumatoid arthritis. The differentiation between primary amy- loidosis and amyloidosis of multiple myeloma is sometimes difficult and artificial because both groups belong to the spectrum of the same funda- mental disease process. However, the lack of ho-

PLEZIA ET AL. 615

FIGURE 2. Top, photo- micrograph showing amy- loid substance and multi- nucleated giant cells. (He- matoxylin and eosin. Magnification, x 800.) Middle, section viewed under polarized light- showing birefringence. (Congo. Magnification, x 800.)

FIGURE 3 (bottom). Electronmicrograph showing nonbranching and randomly oriented fibrils 100 A” in diameter. (Mag- nification, X 30.000.)

616 CHRONIC MUCOCUTANEOUS CANDIDOSIS

Table 1. Manifestations of Amyloidosis

Organ Involvement

Renal Nephrotic syndrome

Cardiac Chronic heart failure Orthostatic hypotension

Neurological Peripheral neuropathy

Gastrointestinal Macroglossia Hepatomegaly with elevation

of liver enzymes Malabsorption

Hematological Anemia Thrombocytosis

Percentage of Cases

32

26 I5

17

20

SO 5

50 5

mogeneous light chain or Bence-Jones protein in urine and serum, plus the lack of characteristic “punched-out” radiolucencies in the skull radio- graph should point toward the primary process.

Despite current advances in understanding of the disease process, the treatment of primary amyloid-

osis has been less than satisfactory. Based on the fact that amyloid fibrils are derived from mono- clonal light chains, the chemotherapeutic treatment of primary amyloidosis has been emphasized, with the use of alkylating agents such as melphalan, col- chicine, or the combination of an alkylating agent and prednisone. In a study of 236 cases at the Mayo Clinic,4 the median survival after initial micro- scopic diagnosis was 14.7 months. Cardiac failure is the number one cause of death in 30% of the cases, followed by renal failure in 13%.

References

I. Eanes ED, Glenner CM: X-ray diffraction studies of amy- loid filaments. J Histochem Cytochem 16:673, 1968

3. Walton AG, Blackwell J: Biopolynes. New York. Academic

Press, 1973 3. Schirahama T, When AS: High resolution electron micro-

scopic analysis of the amyloid fibril. J Cell Biol 33:678. 1967

4. Kyle RA. Bayrd ED: Amyloidosis: review of 236 cases. Medicine 54:27 1. 1975

5. Schwartz Y, Tamse A. Kissin E. et al: An unusual case of temporomandibular joint arthropathy in systemic primary

amyloidosis. J Oral Med 34:40. 1979 6. Glenner GG: Amyloid deposits and amyloidosis-the beta

fibrilloses. New Engl J Med 302:1333. 1980

J Oral Maxillofac Surg

45:616-616.1967

Chronic Mucocutaneous Candidosis in Monozygotic Twins

R. I. MAcLEOD BDS, FDSRCS,* AND A. G. BIRD, BA, BM, BCH, MDt

The chronic mucocutaneous candidoses (CMC) are a rare group of disorders of varying severity characterised by persistent superficial lesions, often with little other susceptibility to infection. The classification of this group of disorders is com- plex and controversial and has been reviewed by Porter and Scully.’ Some varieties show a heredi- tary pattern with an association, in some cases, be- tween CMC and various endocrine defects forming

* Department of Oral Pathology, The Dental School, New- castle Upon Tyne, England.

t Regional Immunology Department, Newcastle General Hos- pital, Newcastle Upon Tyne, England.

Address correspondence and reprint requests to Dr. Mac- Leod: Department of Oral Pathology, The Dental School, Fram- lington Place, Newcastle upon Tyne, NE2 4BW. England.

0278-2391187 $0.00 + .25

the autoimmune polyendocrinopathy-candidosis syndrome (APECS).2

This paper reports a mild variant of CMC af- fecting monozygotic male twins.

Report of Two Cases

Case I

This 26-year-old white male presented with soreness of his mouth and lips that began a few years previously and had since been constant but varying in severity. He also had a thickening of the skin around his fingers that was present since childhood. There was no history of dis- phagia, balanitis, or recurrent respiratory tract infec- tions. Aside from his twin brother, there was no known family history of chronic candidosis.

Examination showed marked angular cheilitis, hyper- keratotic thickening between the finger webs, mild par-