Terence T. Casey

Beta-2 microglobulin is an amyloidogenic protein in man.

Curvilinear fibrils with the tinctorial properties of amyloid were isolated from a patient with bone and joint involvement complicating chronic dialysis for renal disease. Subunit fractions of 24,000 and 12,000 mol wt were identified after gel filtration under dissociating conditions, the latter containing a significant amount of a dimer of the former. This was confirmed by Edman degradation of each fraction, which yielded the amino terminal sequence of normal human beta-2 microglobulin (B2M) to residues 20 and 30, respectively. The size of the subunit protein (12,000 mol wt) and the amino acid composition make it likely that intact B2M is a major constituent of the fibrils. B2M is thus another example of a low molecular weight serum protein, with a prominent beta-pleated sheet structure, that may adopt the fibrillar configuration of amyloid in certain pathologic states.

Tumoral amyloidosis of bone of beta2-microglobulin origin in association with long-term hemodialysis: A new type of amyloid disease

Amyloid lesions of bone are rare and limited almost exclusively to patients with amyloidosis secondary to plasma cell dyscrasias. The present report describes the cases of two patients receiving long-term hemodialysis (nine and 12 years) who had multiple lytic lesions of bone proved by biopsy to contain an unusual type of amyloid. Results of serum protein electrophoreses and immunoelectrophoreses, as well as bone marrow examinations, were normal. In both cases the amyloid displayed characteristic Congo red affinity and birefringence on polarized light microscopy that was inhibited by potassium permanganate treatment of sections prior to staining. Although this staining reaction was described previously exclusively in AA amyloid (i.e., the material associated with classic secondary amyloidosis), immunoperoxidase staining for AA protein in these cases was negative. Transmission electron microscopy revealed the amyloid fibrils to have unusual curvilinear configurations. Immunoperoxidase staining for beta 2-microglobulin (beta 2m) was positive in the amyloid lesions of both patients at the light microscopic level. Ultrastructural immunohistochemical studies for beta 2m, performed in one case, were positive. Both patients had markedly elevated serum beta 2m levels. By Ouchterlony immunodiffusion, purified beta 2m demonstrated partial identity with purified amyloid protein fractions and a serum constituent. Bone lesions composed of amyloid related to beta 2M probably represent a new subgroup of amyloid disease that may be linked to renal failure and long-term hemodialysis.

Clinical Correlates of False-Negative Fine Needle Aspirations of the Breast in a Consecutive Series of 1005 Patients

Fine needle aspiration (FNA) of the breast is a useful diagnostic tool in the management of lesions of the breast. However, false-negatives invariably occur and can detract from the usefulness of the technique. The current study of 16 patients with false-negative FNA of the breast from a consecutive series of 1,005 patients was undertaken in an attempt to better understand the clinical correlates most often associated with false-negative diagnoses. Pre-FNA physical examination and mammographic findings were correlated with the gross and microscopic features of these 16 patients. All 16 patients had palpable findings. Mammographic abnormalities were divided into three categories--highly suspicious for malignant tumor (n = 7), indeterminate (n = 3) and negative (n = 4). Mammograms were not available for two patients. The carcinomas ranged in size from 0.8 to 6.5 centimeters (mean of 1.9 centimeter). Thirteen of 16 carcinomas were 2 centimeters or less. Of the small tumors, histologic factors revealed no special type (NST) in six patients and special type carcinoma in seven patients. The notably large tumor (6.5 centimeters) was of high grade and demonstrated an unusual diffusely infiltrative pattern histologically extending between normal mammary lobules. Overall, special type carcinomas comprised seven of 16 patients. All of these carcinomas, as well as six of nine NST were paucicellular, that is, more than 20 percent area containing tumor cells. The current study supports the findings of others that small tumor size, paucicellularity and special type histologic factors contribute to false-negative diagnoses of FNA of the breast.