Thyroid Nodules May Identify an Aggressive Extramedullary Phenotype in Multiple Myeloma: A Single-Center Case Series

Extramedullary disease (EMD) is a high-risk manifestation of multiple myeloma (MM), reflecting aggressive plasma cell biology, altered tissue tropism, and adverse clinical outcomes. Although thyroid plasmacytomas have been sporadically reported, thyroid nodules in MM are usually considered incidental findings. We aimed to characterize MM patients with thyroid nodules and explore whether this finding may identify a clinical phenotype enriched for extramedullary involvement.

We conducted a retrospective single-center case series of adult patients with MM and documented thyroid nodules identified during routine clinical evaluation or imaging studies. Demographic, clinical, laboratory, imaging, and disease-related variables were collected, including immunoglobulin subtype, CRAB features, renal impairment, osteolytic disease, presence of plasmacytomas, and survival status. Descriptive statistics were used. Exact binomial 95% confidence intervals (CI) were calculated for key clinical outcomes. Because an institutional MM cohort without thyroid nodules was not available, comparative odds ratios were not estimated; instead, this analysis focused on signal detection and phenotype characterization.

Eighteen patients with MM and thyroid nodules were identified. Mean age was 57 years, and 61% were women. IgG MM was the predominant subtype. Concomitant extramedullary plasmacytomas were documented in 33% of patients (95% CI, 13.3-59.0), suggesting enrichment for EMD within this clinically selected cohort. Hypercalcemia and osteolytic lesions were each observed in 17% of cases (95% CI, 3.6-41.4), whereas renal impairment was uncommon, occurring in 6% (95% CI, 0.1-27.3). At last follow-up, 78% of patients were alive (95% CI, 52.4-93.6).

The coexistence of thyroid nodules and plasmacytomas in one-third of patients supports the hypothesis that thyroid abnormalities in MM may not always represent incidental age-related findings. Instead, they may identify a subset of patients with altered extramedullary homing or tissue-invasive biology. The relatively young age of this cohort and the female predominance further highlight the need for dedicated thyroid assessment in MM patients, particularly when thyroid abnormalities coexist with other features suggestive of aggressive disease.

Thyroid nodules may represent an underrecognized clinical finding in MM and could serve as a potential marker of an extramedullary-prone phenotype. Although limited by its retrospective design and absence of an internal comparator cohort, this series demonstrates a clinically meaningful signal, with one-third of patients showing concomitant plasmacytomas. Larger multicenter studies incorporating thyroid imaging, histopathologic confirmation, molecular profiling, and longitudinal outcomes are warranted to determine whether thyroid nodules represent incidental lesions, second primary neoplasms, plasma cell infiltration, or a surrogate marker of aggressive extramedullary disease biology.