Canine extramedullary plasmacytomas are typically benign tumors of the skin, oral cavity, and alimentary tract that are cured by surgical excision. This tumor is rarely metastatic and aggressive. We report an unusual plasmacytoma in a dog that had been presented because of dyspnea. Aside from evidence of pleural effusion, no cutaneous lesions or other abnormalities were detected on physical examination. Nearly 2 L of pleural fluid were removed by thoracocentesis, and a sample was submitted for cytologic examination. The pleural fluid had increased protein and cell concentrations, with a predominance of individualized, large, round, atypical cells. Those cells frequently had Russell body-like intracytoplasmic structures, as seen on microscopic examination of modified Wright-stained concentrated slide preparations. Together, these findings were strongly supportive of a neoplastic plasma cell exudate. Immunohistochemical (CD3, CD20, MUM1, IgG, λ light chain) staining and B-cell PCR for antigen receptor rearrangement analysis performed on formalin-fixed, paraffin-embedded pleural cell-pellet sections confirmed a novel, clonal, IgG lambda extramedullary plasmacytoma with Mott cell differentiation that was most likely metastatic from a non-cutaneous primary site. Metastatic plasma cell neoplasia with voluminous serous cavity effusion carries a grave prognosis in humans, but has not been reported previously in dogs, to our knowledge.

Extramedullary plasmacytoma with rare peritoneal manifestation

Atypical anti-glomerular basement membrane (GBM) nephritis is a rare autoimmune disease characterized by the linear deposition of immunoglobulin G (IgG) detected in the GBM without circulating anti-GBM antibodies or lung involvement. Atypical anti-GBM disease is distinguished from typical anti-GBM disease in both clinical and pathological features. Herein, we report 2 patients who developed mild proteinuria, hematuria, and elevated serum creatinine levels following coronavirus disease 2019 (COVID-19) vaccination. Renal biopsy found bright linear IgG deposition along the GBM, but anti-GBM antibodies were seronegative. Atypical anti-GBM nephritis was determined. The female patient improved with the treatment of valsartan. For the male patient, serum creatinine levels significantly decreased through two plasma exchange sessions, cyclophosphamide, and glucocorticoid. Atypical and typical anti-GBM nephritis are different clinical entities. They target different antigen epitopes and, therefore, atypical anti-GBM disease is not the early stage of typical anti-GBM disease. In atypical anti-GBM nephritis, monoclonal IgG deposition in the glomeruli is not equal to plasma cell dyscrasias but still needs close monitoring for hematologic diseases. The relationship between the disease and COVID-19 vaccination is uncertain and needs further exploration.

Using suboptimal imaging modalities on the detection of bone and extra-bone myeloma lesions affects disease status recognition and early treatment decisions. Moreover, a systematic search of the evidence was not provided alongside the recommendations. The objective of this study was to assess the current real world imaging practices in Italy, influencing factors, and barriers to adopting international imaging guidelines for MGUS and MM (reported as plasma cell disorders, PCD) and to develop evidence-based, country-specific recommendations for imaging assessment of PCD patients. A national project was launched in 2024, involving experts from 32 hematology centers and 5 radiology services. A survey was conducted and a Delphi panel comprising 23 experts was used to reach a consensus on the developed recommendations. A total of 25 recommendations were finally formulated. The survey revealed that suboptimal imaging modalities were significantly contributing to the under-recognition of bone and extra-bone lesions in myeloma, leading to suboptimal disease status assessment and treatment decisions. The study emphasizes the importance of adopting effective imaging modalities to improve disease detection and guide treatment decisions in PCD patients. A country-specific, evidence-based set of imaging recommendations has been developed to address existing challenges in the adoption of international imaging guidelines.

Monoclonal gammopathy of undetermined significance (MGUS) is a necessary precursor of multiple myeloma (MM). Compared to non-Hispanic Whites (Whites), African Americans experience about 2-fold greater, and Asian Americans 50% lower, occurrence of MGUS and MM. We examined determinants of MGUS and progression to MM or other plasma cell neoplasms (PCN) among Japanese American, African American, Latino, Native Hawaiian, and White participants in a case-control study nested in the Multiethnic Cohort (MEC) Study. Presumptive cases included MEC participants 65+ years old initially screened using the Medicare billing code for paraproteinemia along with those with MM/PCN at least one year after blood draw. Presumptive controls had no Medicare billing code or MM. Laboratory confirmation resulted in 426 confirmed MGUS cases (370 non-IgM and 56 IgM) and 863 MGUS-free controls. We used multivariable logistic regression and Cox regression to estimate associations with MGUS and MGUS progression. The distribution of immunoglobulin (Ig) isotypes differed by race/ethnicity (P=0.005): Japanese Americans had the lowest (11.0%) and Native Hawaiians the highest (23.5%) proportion of IgA. Each unit increase in BMI (kg/m2) was associated with a 6% increase in non-IgM MGUS (95% CI= 3-9%) among all racial/ethnic groups combined. BMI was also significantly associated within most racial/ethnic groups, especially among Native Hawaiians (13% increase per BMI unit), and with IgA and IgG MGUS. Progression to MM or other PCN was associated with an M-spike >1.5 g/dL, but not with BMI. BMI was the main determinant associated with MGUS, but not with progression. Isotype distribution differed between racial/ethnic groups.

Russell body gastritis is a discrete morphologic pattern of chronic gastritis, characterized by numerous plasma cells filled with intracytoplasmic Russell body inclusions. It can be mistaken for neoplastic lesions and for extracellular hyaline structures. We report three adult men with Russell body gastritis. The patients were diagnosed and treated for various hematolymphoid disorders. During follow-up, they presented with abdominal pain, gastric erythema and thickening. One patient had Helicobacter pylori infection. The gastric biopsy showed an expanded lamina propria filled with numerous plasma cells containing hyaline glassy globules. Initial hematoxylin and eosin impression included amyloidosis, gastric antral vascular ectasia, neuroendocrine tumor, plasma cell neoplasm and low-grade lymphoma with plasmacytic features. The inclusions showed a homogenous magenta staining pattern with periodic acid-Schiff and diastase, a central dark red core surrounded by a bluish ring with Masson trichrome, and were apple-green with mucicarmine. Although they showed an orangeophilic amyloid-like staining pattern with Congo red, they were not birefringent. The inclusions were metachromatic and nested in clefted lacunar spaces. The plasmacytoid and rhabdoid cells expressed CD45, CD38, CD138, CD79a and epithelial membrane antigen. They were polytypic with kappa and lambda light chains. The immunomarkers showed a characteristic reticulated network surrounding the inclusions, creating a negative image. Russell body gastritis is a rare and special form of chronic gastritis. It can be mistaken for various lesions. Histochemical and immunohistochemical stains are useful ancillary diagnostic tools. The occurrence of this phenomenon in certain patients with compromised immune systems is clinically significant and requires validation.

Tumor Treating Fields (TTFields) are approved for glioblastoma (GBM) treatment, but predictive biomarkers remain unclear. This study evaluates TTFields effectiveness in primary GBM cell cultures and explores miRNA biomarkers in tumor tissue, plasma, and primary cell cultures. TTFields were applied to 21 primary GBM cell cultures for 72 h. Cell viability was assessed pre- and post-treatment, with parallel evaluations in control cultures. Expression levels of miRNAs-21, -26a, -34a, -181c, -181d, and -485-5p were analyzed in tumor tissue, plasma, and untreated/treatment-exposed cultures. Correlation analyses examined TTFields response and miRNA expression. Response rates varied, with a mean cell viability reduction of 48.53%. Expression of miRNA-26a in tumor tissue (p = 0.041, r = 0.502) and miRNAs-21, -26a, and -181c in untreated control cultures (p < 0.05) correlated with increased TTFields effectiveness. Linear correlations were observed for miRNAs-26a and -181c in untreated control cultures ([95% CI: 0.001938-0.01725, p = 0.016; 95% CI: 0.0000003935-0.0001641, p = 0.049). Individual GBM cell cultures respond differently to TTFields. Overexpression of miRNA-26a in native tumor tissue and overexpression of miRNAs-21, -26a and -181c in untreated control cell cultures were positively correlated with increased effectiveness of TTFields treatment.

A diverse spectrum of clonal disorders arising from terminally differentiated B cells that secrete monoclonal immunoglobulins or their components is collectively referred to plasma cell dyscrasias (PCDs). Clinical presentations vary widely, from early asymptomatic stages such as monoclonal gammopathy of undetermined significance, to organ-damaging conditions including multiple myeloma, AL amyloidosis, Waldenström macroglobulinemia, and other less common plasma cell related syndromes. Accurate laboratory diagnosis is essential because early recognition of monoclonal proteins can prevent irreversible organ damage involving bone, kidney, or hematopoietic systems. This review summarizes current laboratory diagnostic approaches for PCDs and discusses key differential diagnosis across major PCD entities. A narrative literature research was performed using open-access databases (PubMed, Scopus, ScienceDirect, and Google Scholar), focusing on publications from 2015-2025 addressing diagnostic modalities, disease-defining criteria, and distinguishing features relevant to clonal and reactive plasma cell processes. Findings highlight that optimal diagnosis relies on integrating serum and urine studies, immunofixation, serum free light chain assay with immunophenotyping, cytogenetic profiling, and bone marrow assessment. Flow cytometry enables clonal confirmation through aberrant plasma cell immunophenotypes, whereas FISH identifies recurrent genomic abnormalities with prognostic relevance. Molecular assays provide additional refinement in selected cases. Accurate interpretation requires correlation with clinical features to differentiate PCDs spectrum. A structured, multimodal diagnostic strategy is essential for precise classification, risk stratification, and guiding patient management across diverse healthcare settings.

Primary plasma cell leukemia (pPCL) represents the most aggressive plasma cell dyscrasia with a poor prognosis and survival of <3 years. The International Myeloma Working Group (IMWG) adopted more inclusive diagnostic criteria for pPCL in 2021, including patients with 5% or more circulating plasma cells (down from 20%). Most published studies of pPCL do not include patients who meet the criteria for pPCL based on the newer diagnostic guidelines, and the data on the optimal treatment of pPCL is scarce. In our multi-center retrospective analysis, we report data on treatment regimens used in 67 pPCL patients to characterize outcomes in this population. We included patients with newly diagnosed pPCL between 2010 and 2023 based on the 2021 IMWG definition at one of three academic centers. Our results suggest significant improvement in overall response rate (ORR) and progression-free survival (PFS) with the use of autologous stem cell transplant, but without additional benefit for a tandem transplant. The presence of high-risk cytogenetics was an independent risk factor for progression in the cohort. Our dataset represents one of the largest cohorts to date using the expanded definition of pPCL adopted by the IMWG in 2021 and stresses the importance of taking pPCL patients to transplant. Unfortunately, our study was not powered to determine the efficacy of individual induction and maintenance regimens, and many patients diagnosed with pPCL are ineligible for transplant based on end-organ damage at diagnosis or from disease that is refractory to induction therapy, underscoring the need for early diagnosis and treatment in hopes of preserving transplant eligibility.

Here we assess the diagnostic features of 73 canine extramedullary plasmacytomas (EMPs) and their differentiation from canine cutaneous histiocytomas (CHs) using histology and immunohistochemistry for MUM1, CD3, CD79a, immunoglobulin (Ig) light chains (λ and κ), and IBA1. Most EMPs were classified as cleaved and mature subtypes. Almost 92% of EMPs were positive for MUM1, whereas 77% were positive for CD79a and 74% for Ig light chains λ and κ. The use of MUM1 and Ig light chains resulted in a sensitivity of 100% in diagnosing EMPs, surpassing the combination of MUM1 and CD79a (94%). In 8% of the EMPs, there was pseudofollicular arrangement of neoplastic cells, whereas 7% had amyloid deposition and 3% had mineralization. CHs were positive for IBA1 but negative for all other IHCs.

The WHO categorises plasma cell tumours into two primary types: multiple myeloma and plasmacytoma. Plasmacytoma is further classified into solitary extramedullary plasmacytoma (EMP) and solitary plasmacytoma of bone. The upper respiratory tract and nasopharynx are the sites most commonly affected by EMP. Gastrointestinal tract involvement occurs in approximately 10% of EMP cases, while colonic involvement-particularly when associated with intussusception-is exceedingly rare. We present the case of a middle-aged man in his 40s who reported haematochezia, fatigue and weight loss over a 6-month period, without fever or bone pain. Physical examination revealed pallor. Endoscopic evaluation demonstrated a polypoidal mass at the hepatic flexure of the colon. An initial biopsy suggested a neuroendocrine tumour. Based on this provisional diagnosis, a D3 right extended hemicolectomy was performed. However, subsequent histopathological analysis unexpectedly revealed plasmacytoid cells consistent with EMP.

This review examines the complex bidirectional relationship between vasculitis and hematologic malignancies, highlighting the importance of meticulous diagnostic assessment. Vasculitis may emerge in the setting of hematologic malignancies via mechanisms such as paraneoplastic inflammation, immune dysregulation, drug exposure, and clonal hematopoiesis. Myeloid neoplasms - especially myelodysplastic syndrome (MDS) and chronic myelomonocytic leukemia (CMML) - show a stronger association than lymphoid malignancies, with cutaneous small vessel vasculitis being the most common subtype. VEXAS syndrome exemplifies the overlap between autoinflammation and hematologic disease, often presenting with vasculitic features and macrocytic anemia.In lymphoproliferative disorders and plasma cell dyscrasias, vasculitis may precede, mimic, or complicate the malignancy. Entities such as intravascular lymphoma, angioimmunoblastic T-cell lymphoma, and monoclonal gammopathies - including MGUS and multiple myeloma - can manifest with vasculitic symptoms, requiring histopathologic and molecular evaluation. Emerging concepts like monoclonal gammopathy of cutaneous and rheumatologic significance highlight the need for interdisciplinary care.Drug-induced vasculitis, particularly from immunomodulatory agents and biologics, adds diagnostic complexity. Atypical features - such as unexplained cytopenias, dual autoantibody positivity, or poor response to immunosuppression - should prompt evaluation for underlying hematologic disease. Conversely, vasculitis may signal complications in patients with known hematologic disorders. Early suspicion of vasculitis associated with hematologic malignancies and accurate diagnosis are important in guiding therapeutic approaches.

Within- and Between-Subject biological variation estimates of serum free light immunoglobulin chains in healthy individuals in Turkey.

Rare Head and Neck Tumors: An Imaging Review.

Primary lung extramedullary plasmacytoma mimicking tumor recurrence: A case report

Background: Routine assessment of renal biopsies requires staining with Congo Red staining for amyloidosis as well as immunofluorescence staining for kappa and lambda to detect monoclonal gammopathies. Correlating with histopathology, we can diagnose the nature of renal involvement of plasma cell dyscrasias, which may be in the form of myeloma cast nephropathy, light chain deposition disease, interstitial nephritis, and toxic tubulopathy. If there is nodular glomerulosclerosis which may resemble diabetic kidney, combination of Congo Red and kappa/lambda can be helpful in diagnosis of AA vs AL amyloidosis. Method: On retrospective analysis of all renal biopsies received over 2017-2024, a total of 12 cases were finalized out of 824 total renal biopsies. The biopsies had undergone the usual processing with routine stains and immunofluorescence studies. Cases were diagnosed with the help of clinical features, biochemical findings, histopathological analysis and immunofluorescence studies. Result: Patients with either amyloidosis or kappa/lambda monoclonality were more commonly males with median age of 62.5 years and increased creatinine level. Nephrotic syndrome was the most common clinical presentation. Myeloma cast nephropathy, light chain deposition disease and nodular amyloidosis were the most common histopathological diagnoses and lambda was more commonly predominant on immunofluorescence. Conclusion: Immunofluorescence with kappa/lambda is essential in the diagnosis of renal involvement by myeloma which may precede, occur simultaneously, or follow bone marrow involvement.

This case report presents a 55-year-old female with concurrent pauci-immune crescentic glomerulonephritis (PICGN) and monoclonal gammopathy of undetermined significance (MGUS), highlighting the diagnostic challenges in differentiating between monoclonal gammopathy of renal significance (MGRS) and MGUS in the context of ANCA-associated vasculitis (AAV). The patient presented with acute kidney injury, proteinuria, and hematuria, with renal biopsy revealing type III crescentic glomerulonephritis and immunofluorescence showing weak positivity for κ and λ monoclonal immunoglobulin deposits. Despite initial suspicion of MGRS, immuno-electron microscopy did not confirm monoclonal light chain deposition, leading to a final diagnosis of PICGN and MGUS. The patient was treated with glucocorticoids and cyclophosphamide, resulting in stabilization of renal function but necessitating maintenance hemodialysis due to irreversible renal damage. This case underscores the importance of integrating serological, histopathological, and advanced imaging techniques to distinguish between autoimmune and plasma cell dyscrasias in renal pathology. It also emphasizes the limitations of immunofluorescence alone in diagnosing MGRS and the necessity of immuno-electron microscopy for definitive exclusion. This report calls for further research into the pathophysiological interactions between AAV and monoclonal gammopathies, particularly in cases with overlapping renal injury features.

Multiple myeloma (MM) is a plasma cell dyscrasia sustained by the clonal proliferation of plasma cells within the bone marrow. MM represents the second most common hematologic neoplasm and, despite the continuous effort to overcome this disease, it remains an uncurable disease. Throughout the recent years, novel therapeutic targets have been investigated, leading to the development of novel treatments for MM patients. In the last ten years, the interest for the long non-coding RNA NEAT1 has significantly grown within the field of cancer, including MM. In this review we offer a panoramic view of the role of NEAT1 in MM, with a focus on its possible role as both biomarker and therapeutic target.

Extramedullary plasmacytoma (EMP) is a rare plasma cell malignancy, comprising a small subset of plasma cell neoplasms. It can occur as a solitary lesion in bone (bone plasmacytoma) or soft tissue (extramedullary plasmacytoma). Many clinicians are not yet aware that cases of extramedullary plasmacytoma can be transform into plasmablastic myeloma, which has a poor prognosis. A 35-year-old male presented with progressive weakness and a persistent cough. Clinical examination findings: in the thoracic area showed a lumpy, immobile mass measuring approximately 15 cm was found in the left thoracic region. Imaging showed a destructive mass in the left posterior thoracic wall, measuring 17.72 cm×15.74cm×16.83 cm. Fine Needle Aspiration Biopsy (FNAB) confirmed extramedullary plasmacytoma. Bone marrow aspiration revealed 92% plasmablast cells, suggesting possible transformation to plasmablastic myeloma. Immunophenotyping showed positive for CD138 and CD56, but negative for CD34, CD19, CD20, CD79a, CD33, and CD13. Protein electrophoresis showed monoclonal gammopathy. Transformation of extramedullary plasmacytoma into plasmablastic myeloma is rare but clinically significant. This case emphasizes the importance of thorough diagnostic evaluation, including bone marrow aspiration and immunophenotyping, to detect early disease progression. Immunophenotypic markers, such as CD138 and CD56 positivity with CD34, CD19, and CD20 negativity, aid in diagnosis. Early detection of transformation is crucial for timely treatment due to the aggressive nature of plasmablastic myeloma. This case underscores the need for close collaboration between clinicians and pathologists to ensure early detection of EMP transformation into plasmablastic myeloma. Comprehensive diagnostic workup, including bone marrow aspiration and immunophenotyping, is essential to guide appropriate clinical management

Central nervous system (CNS) involvement in plasma cell neoplasms is rare and associated with poor prognosis, and indications for cerebrospinal fluid (CSF) analysis remain undefined. We describe three cases: two with advanced-stage, high-risk cytogenetics, and one stage I case meeting criteria for plasma cell leukemia (PCL). In two patients, delayed CSF evaluation after neurological symptoms led to rapid deterioration, whereas early CSF analysis in an asymptomatic patient enabled timely diagnosis. One case worsened acutely after treatment with plerixafor. These findings suggest that CSF evaluation may merit consideration in high-risk patients, including those with PCL or before plerixafor administration.