American journal of clinical pathology
July 1, 2026 · via Europe PMC
Clinicopathologic characterization of plasma cell neoplasms with IGH::CCND3.
Padmanabha N, Sperling AS, Morgan EA, Michaels PD, Sadigh S.
AI summary — for doctors, generated from the abstract only
A study of a rare genetic subtype of plasma cell cancer (multiple myeloma and related conditions) found it frequently shows distinctive features resembling a different, more common cancer subtype, and that a specific immunohistochemistry test can reliably flag these cases, helping ensure they get the correct genetic testing rather than being miscategorized.
What was studied
A study identifying 16 patients with plasma cell neoplasms carrying a rare genetic abnormality called IGH::CCND3, analyzing their clinical, microscopic, immune marker, and genetic features, and evaluating whether an immunohistochemistry test for cyclin D3 protein could reliably identify these cases.
Key findings
- Among the 16 patients (median age 68.9), diagnoses included multiple myeloma (9), monoclonal gammopathy of undetermined significance (3), smoldering myeloma (2), plasma cell leukemia (1), and amyloid light chain amyloidosis (1); most cases (63%) showed a specific microscopic appearance resembling lymphoma, with frequent expression of CD20 (53%) and aberrant expression of CD56 (71%) and CD117 (69%).
- Loss of an entire copy of chromosome 13 was the most common additional genetic abnormality (50% of cases).
- Cyclin D3 immunohistochemistry showed positive nuclear staining in the cancerous plasma cells in all 11 tested patients, and when combined with another marker (CD138) in a dual stain, proved highly sensitive and specific for identifying these neoplastic cells.
Clinical relevance
The findings suggest that plasma cell neoplasms with this rare genetic abnormality often resemble a more common, different genetic subtype under the microscope, and recommend using cyclin D3 immunohistochemistry specifically in cases with this lymphoma-like appearance but negative for the more common marker (cyclin D1), to appropriately trigger confirmatory genetic testing and avoid these cases being miscategorized or missed entirely.
Who should care
Limitations
This is a relatively small case series (16 patients) of a rare genetic subtype, so broader validation of the cyclin D3 testing approach in additional independent cohorts would further support its routine diagnostic use.
A rare genetic subtype of plasma cell cancer frequently resembles a different, more common cancer subtype under the microscope, but a specific immunohistochemistry test (cyclin D3) can reliably flag these cases, helping ensure patients receive the correct genetic testing and diagnosis.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Objectives
Plasma cell neoplasms (PCNs) harboring IGH::CCND3 (t(6;14)) are rare (<1% of PCNs). We sought to study these cases, as they have not been studied as a distinct entity, and their clinicopathologic features are not well characterized.
Methods
Cytogenetics databases were searched for positive IGH::CCND3 interphase fluorescence in situ hybridization (FISH) results in plasma cell neoplasms. We analyzed the clinical, morphologic, immunophenotypic, and cytogenetic features of these cases and evaluated the utility of cyclin D3 immunohistochemistry (IHC) for identifying these neoplasms.
Results
Sixteen patients were identified, presenting with multiple myeloma (n = 9), monoclonal gammopathy of undetermined significance (n = 3), smoldering myeloma (n = 2), plasma cell leukemia (n = 1), and amyloid light chain amyloidosis (n = 1). Median age at diagnosis was 68.9 years. Most cases showed lymphoplasmacytoid morphology (63%, 10/16), with frequent CD20 expression (53%, 8/15) and aberrant expression of CD56 (71%, 10/14) and CD117 (69%, 9/13). Monosomy 13 was the most frequent concurrent cytogenetic abnormality (50%, 7/14). Cyclin D3 IHC showed nuclear expression in plasma cells in all tested patients (11/11). Background erythroid precursors and megakaryocytes also showed variable positivity. When performed as a dual immunostain with CD138, cyclin D3 served as a highly sensitive and specific method for detecting these neoplastic plasma cells.
Conclusions
IGH::CCND3 PCNs frequently exhibit lymphoplasmacytoid features and CD20 expression, resembling the more common t(11;14) PCNs. Cyclin D3 IHC is an effective surrogate for the t(6;14) translocation in PCNs. We recommend using cyclin D3 IHC in the workup of PCNs with lymphoplasmacytoid morphology but negative cyclin D1 to appropriately trigger reflex FISH testing in positive cases and rescue them from the "partner-negative" category.
DOI
10.1093/ajcp/aqag080
PMID
42418658
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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