THE purpose of this article is primarily to review the more recent acquisitions to the knowledge and understanding of the pathophysiology of the plasma-cell dyscrasias. Several comprehensive studies of the clinical, radiographic, pathological and biochemical features of multiple myeloma have been published in the past thirty years.1 2 3 4 5 6 7 8 9 10 11 12 13 Major emphasis in this presentation, however, will be given to specific topics pertaining to plasma-cell neoplasia in which recent progress has been made. The "typical" case of multiple myeloma, if, indeed, such an entity exists, must now be considered as representing just one of several clinical patterns that may arise from a primary . . .

Plasma-cell myeloma. II. Clinical aspects.

Much has been written about disorders of nervous function due to tumours of the plasma cell type (plasmacytoma and multiple myeloma). Detailed discussions of this subject and reviews of the literature are to be found in the monograph of Snapper, Turner, and Moscovitz (1953), and in the comprehensive articles of Geschickter and Copeland (1928), Davison and Balser (1937), Shenkin, Horn, and Grant (1945), and Bayrd and Heck (1947). These writings make repeated reference to several syndromes resulting from compression of neural structures by masses of tumour tissue. By far the best known of these is " myelomatous paraplegia " due to compression of the spinal cord by extradural deposits of myeloma and occasionally by a collapsed vertebra. Similarly, nerve roots and peripheral nerves may be compressed by myelomatous tissue extending from contiguous bone. Cranial nerve palsies may result from myelomatous compression at their foramens of exit at the base of the skull and less commonly there may be neoplastic invasion of intracranial or intraorbital structures. These orbital and intracranial complications of multiple myeloma have recently been reviewed by Clarke (1953, 1954). Herpes zoster is a rare complication of multiple myeloma (Anders and Boston, 1903; von Bomhard, 1914; Wallgren, 1920) and, most recently, median neuritis due to amyloid deposition in the carpal ligament has been describedt (Grokoest and Demartini, 1954). The topic to which we invite attention is a curious and little known affection of peripheral nerves which is only obscurely related to multiple mycloma, for the disease, unlike the aforementioned neurological syndromes, does not in any way depend on compression of nervous structures by tumour tissue.

https://jnnp.bmj.com/content/jnnp/21/2/73.full.pdf

The neuropathy of multiple myeloma

Although the nervous system manifestations of multiple myeloma have been described previously, 1-9 there still remains some controversy concerning the incidence, pathogenesis, and treatment of the several types of neurologic complications of the disease. Many of the previous publications of the neurologic aspects of myelomatosis were based on observations of small series of patients who were sometimes specially selected (eg, those admitted to a neurosurgical service). The emphasis of many of the previous reports has been either on the direct compression of the nervous system by myeloma tumor or on distant "toxic" effects. In the older literature, the criteria for the diagnosis of multiple myeloma have, at times, also been uncertain. The purpose of this communication is to report and discuss the neurologic complications observed in 277 patients admitted to a general hospital, where a diagnosis of multiple myeloma was eventually proved. Materials and Methods The 277 patients were all

Neurologic Complications of Myelomatosis

1 61-year-old man had osteosclerotic myeloma that was localized in the eleventh thoracic vertebral body and associated with sensorimotor polyneuropathy, skin hyperipigmentation, edema, hypertrichosis, gynecomastia, and white nails. Cases of osteosclerotic myeloma with and without polyneuropathy in the literature were reviewed with special reference to accompanying dermatologic and endocrinologic signs and synmptoms. We assume that the polyneuropathy, cutaneous hyperpigmentation, edema, hypertrichosis, gynecomastia, and white nails are causally related to each other and are a remote effect of osteosclerotic myeloma. Quantitative histologic analysis of two sural nerves biopsied within 2 years of each other during the course of the disease indicated that both large and small myelinated fibers degenerated progressively, with relative preservation of unmyelinated fibers.

Polyneuropathy, skin hyperpigmentation, edema, and hypertrichosis in localized osteosclerotic myeloma.

Recently attention has been directed to the various non-metastatic neurological manifestations of malignant diseases, and myeloma, noted for its presentation by signs of compression and infiltration, is less widely known in association with chronic symmetrical polyradiculoneuropathy. This paper discusses certain clinical aspects of this neuropathy. We have found 16 accounts of the association with multiple myeloma (Table I), and seven with 'single' myeloma (Table II). These numbers do not include certain other reports (Kurnick and Yolahem, 1948, cases 1 and 3; Madonick and Solomon, 1953; Victor, Banker, and Adams, 1958, case 5; Williams, Diamond, Craver, and Parsons, 1959, case J. G.; Barron, Rowland, and Zimmerman, 1960; and Bibliography-1'2), some of which do not describe the cases; in some the clinical picture was complicated by myelomatous compression or infiltration, or amyloid deposition, and in some the neuropathy was not a chronic symmetrical polyradiculoneuropathy. In two recent descriptions the writers comment on the unusual osteosclerotic myeloma in their cases (Small, Moxon, and Woolf, 1961; Aguayo, Thompson, and Humphrey, 1964), and ask whether this is more than a chance association. By reporting four more cases and reviewing the literature, we conclude that this concurrence is significant. In addition, our observations indicate that if the myeloma can be controlled, this otherwise fatal neuropathy is reversible.

https://jnnp.bmj.com/content/jnnp/30/5/432.full.pdf

The relation between chronic polyneuropathy and osteosclerotic myeloma.

THERE that the typical and characteristic lesion of bone in multiple myeloma is a discrete osteolytic involvement. The roentgenographic appearance is usually that of a punched-out area with sharp margination and without evidence of surrounding productive reaction. In a description of multiple myeloma Boyd 1 stated, "It is a pure rarefying lesion with no formation of new bone." To quote Geschichter 2 : "The widespread occurrence of small, sharply demarcated defects in the marrow cavity, unaccompanied by bending deformity or the formation of new bone, are the cardinal features in the diagnosis of multiple myeloma." Snapper 3 affirmed that in multiple myeloma "no new formation of bone takes place." Shanks, Kerley and Twining 4 declared categorically concerning the osseous lesions of multiple myeloma that "they are entirely osteolytic, and never give rise to new bone formation." The case to be presented is of unusual interest because it has been possible to

https://jamanetwork.com/HttpHandlers/ArticlePdfHandler.ashx?journal=INTEMED&articleId=554512&pdfFileName=archinte_84_6_010.pdf

Ammiel Smelin

Papers

Multiple myeloma with new bone formation.