Tracing the Origins of Myeloma Terminology and Its Limitations

Multiple myeloma, one of the most common blood cancers treated by haematologists, carries a name that is scientifically misleading, historically accidental and linguistically convoluted. A new review published in the open-access journal eJHaem traces the tangled origins of myeloma-related terminology, from the Greek suffix “-oma” to the alphabetical jumble of immunoglobulin classes, and asks whether the language of myeloma medicine is overdue for an update. The answer, according to the authors, is that the disease was named twice over—once for bone marrow tumours that often are not there, and once by a pathologist working in Kyiv whose contribution has been all but forgotten.

The suffix “-oma,” of Greek origin (-ωμα), originally denoted a process or action rather than a tumour. According to the Oxford English Dictionary, early English uses of the suffix had nothing to do with cancer at all. A “diploma” was once a double-folded paper, with the “-oma” referring to the action of folding, while a “scotoma” described a process of darkening before it became a neurology term. It was only from the nineteenth century onward that pathologists began attaching “-oma” to words to denote tumours, particularly malignant neoplasms. In that spirit, “myeloma” should ideally mean multiple tumours of the bone marrow—the prefix “myelo-” refers to marrow, or to the spinal cord, which ancient observers mistook for a peculiar form of marrow because it is encased by the vertebral bodies. That same linguistic overlap sometimes causes confusion today between myeloma and myeloid neoplasms such as myelodysplastic syndromes, two entirely different families of disease.

The first recorded use of “multiple myeloma” came in 1873 from a relatively obscure pathologist named von Rusitzky, working in Kyiv. He described eight separate bone tumours thought to arise from the marrow in a 47-year-old patient who presented with swelling of the temple, sternum and ribs. Von Rusitzky argued that the microscopic and macroscopic characteristics of these tumours justified classifying them as a special class and naming them “myelomas,” to denote the similarity of their structure to bone marrow. Yet the disease itself had already been recognized decades earlier under an entirely different name, and through an entirely different body fluid.

In the 1840s, the London physician Macintyre encountered a patient named Thomas Alexander McBean, who presented with pathological fractures and oedema. McBean’s urine had an unusual property: it stiffened his body linen despite the absence of any urethral discharge, and it had a strikingly high specific gravity. The urine was analysed by Henry Bence Jones, widely regarded as the best “chemical doctor” in London, who found a precipitate with unique thermal properties. He concluded that the protein was “hydrated deutoxide of albumen”—a reasonable guess for the era, when most urinary proteins were called albumen, but wrong. The protein that now bears Bence Jones’s name had no relation to albumen at all. Macintyre and Bence Jones urged clinicians to look for this “albumen oxide” in all cases of “mollities ossium,” the Latin term for soft bones that resembles the modern term osteomalacia and was once applied to many forms of bone disease. What would later be called myeloma was thus initially diagnosed on the basis of Bence Jones proteinuria accompanied by bone changes—no marrow tumours required.

Eponyms further muddied the terminology. In some countries, the disease was named after physicians who published influential early descriptions. “Kahler disease” gained currency after an 1889 report of a physician with myeloma by the Vienna-based pathologist Otto Kahler, and in Italy “Kahler-Bozzolo disease” recognized an 1897 paper by the Turin pathologist Camillo Bozzolo. Remarkably, “Kahler disease” still maps to myeloma (code C90.0) in the tenth edition of the International Classification of Diseases, persisting in electronic medical records and databases built on ICD-10 or its earlier versions.

The term “paraprotein,” central to modern myeloma practice, was introduced in 1940 by the pathologist Apitz at Charité Hospital in Berlin, a few years before he died in an air raid. Writing about protein metabolism disorders in plasmacytoma carriers, Apitz proposed the term for a group of closely related pathological protein products occurring in plasmacytoma that were easily degradable and readily crystallizable—proteins produced “parallel” to other proteins. The Swiss pathologist Roulet and colleagues later argued that “paraprotein” was justified whenever an identified protein differed qualitatively from normal serum proteins. Database searches of published text show that the use of “paraprotein” has climbed steadily since 1940, while “dysproteinemia,” coined in 1945 by the Swiss pathologist Ferdinand Wurhmann to emphasize abnormal blood proteins, is steadily falling out of favour. Another legacy term, “plasma cell dyscrasia,” draws on the Greek “krasis” meaning mixture, and harks back to the ancient idea of disease as a bad mixture of bodily humours.

Understanding what paraproteins actually were required three Swedish Nobel laureates whose work mostly predated Apitz’s term. Svante Arrhenius, awarded the Nobel Prize in Chemistry in 1903, showed in the 1880s that dissolved salts dissociate into positive and negative ions that conduct electricity. Theodor Svedberg, the 1926 chemistry laureate, continued the study of colloidal solutions in Arrhenius’s laboratory and developed the ultracentrifuge for separating proteins and determining their molecular weights. Arne Tiselius, laureate in 1948, began as Svedberg’s assistant and showed that purified proteins migrate as homogeneous bands in an electric field. Tiselius’s U-tube electrophoretic apparatus, which created sharp boundaries between protein and buffer solutions, revealed four distinct bands in horse serum: albumin plus three others he named alpha, beta and gamma. Working with Kabat in New York, Tiselius demonstrated that the gamma fraction of serum carries the maximum amount of immunoglobulin—hence “IgG,” the G denoting gamma. The method, later simplified to use filter paper, was adopted worldwide and transformed the study of myeloma patients.

The remaining immunoglobulin names are a patchwork of accident and compromise. In 1944, Waldenström described two patients with abnormal serum proteins but no bony lesions—what he called “myeloma without myeloma”—and identified macroglobulins, now known as IgM. His recognition of abnormal gamma-band proteins in apparently healthy people led, via a seminal 1978 paper by Kyle at the Mayo Clinic, to the term “monoclonal gammopathy of undetermined significance,” or MGUS, which along with Kyle’s coinage “smouldering myeloma” continues to evolve—recent efforts have sought to rename a subset as “monoclonal gammopathy of clinical significance.” A third immunoglobulin, originally called beta-2-A globulin, was truncated to IgA, even though no globulins were ever identified in the alpha region of the electrophoretic peak. IgD’s discoverers, Rowe and Fahey in Bethesda, wanted to call it IgB, but that name had been reserved for murine beta-globulin, and IgC was unavailable because the letter C has no direct Greek equivalent—so IgD it was. The allergy-related immunoglobulin IgE was isolated by the husband-and-wife team Kimishige and Teruko Ishizaka, originally from Tokyo and working in Denver, from the serum of a person highly sensitive to ragweed pollen; the “E” stands for erythema, reflecting the skin-sensitizing properties they were studying. The World Health Organization standardized this irregular nomenclature in 1964.

Even the light chains carry hidden names. In the 1950s, Korngold and Lipari in New York used immunodiffusion to study the antigenic relationships between Bence Jones proteins, myeloma globulins and normal gamma globulin, concluding that Bence Jones proteins are produced by cells incapable of synthesizing the complete myeloma globulin, with the smaller incomplete proteins excreted in urine. The two distinct protein types they identified were named kappa and lambda—the Greek letters K and L—after the first letters of Korngold’s and Lipari’s surnames, and only later understood to be the lower-molecular-weight light chains of normal immunoglobulin. Even “plasma cell” is a historical accident: Waldeyer-Hartz in Berlin, better known for coining “neuron,” provisionally named large, protoplasm-rich cells in connective tissue “plasma cells” in the era of the Protoplasm Doctrine, when all living cells were believed to be made of protoplasm. His cells may actually have been mast cells; true plasma cells were first clearly described by Santiago Ramón y Cajal. Plasma cells, in other words, have nothing to do with blood plasma.

Today, myeloma is diagnosed by evidence of increased clonal plasma cells combined with myeloma-defining events such as organ damage and a high serum free light chain ratio—not by finding multiple tumours of the bone marrow, as in the nineteenth century. The authors note that language, once established, resists revision: influenza is not caused by stellar “influence,” and malaria is not caused by bad air, yet those names persist. The immunoglobulin alphabet, irregular as it is, seems here to stay. Whether myeloma itself should be renamed—and what it would be called instead—remains an open question, but the review makes clear that every familiar term in the myeloma clinic carries a story of incomplete science, lucky guesses and linguistic inertia.