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Handbook of Clinical Neurology 2024Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality... (Review)
Review
Peripheral neuropathy is a common referral for patients to the neurologic clinics. Paraneoplastic neuropathies account for a small but high morbidity and mortality subgroup. Symptoms include weakness, sensory loss, sweating irregularity, blood pressure instability, severe constipation, and neuropathic pain. Neuropathy is the first presenting symptom of malignancy among many patients. The molecular and cellular oncogenic immune targets reside within cell bodies, axons, cytoplasms, or surface membranes of neural tissues. A more favorable immune treatment outcome occurs in those where the targets reside on the cell surface. Patients with antibodies binding cell surface antigens commonly have neural hyperexcitability with pain, cramps, fasciculations, and hyperhidrotic attacks (CASPR2, LGI1, and others). The antigenic targets are also commonly expressed in the central nervous system, with presenting symptoms being myelopathy, encephalopathy, and seizures with neuropathy, often masked. Pain and autonomic components typically relate to small nerve fiber involvement (nociceptive, adrenergic, enteric, and sudomotor), sometimes without nerve fiber loss but rather hyperexcitability. The specific antibodies discovered help direct cancer investigations. Among the primary axonal paraneoplastic neuropathies, pathognomonic clinical features do not exist, and testing for multiple antibodies simultaneously provides the best sensitivity in testing (AGNA1-SOX1; amphiphysin; ANNA-1-HU; ANNA-3-DACH1; CASPR2; CRMP5; LGI1; PCA2-MAP1B, and others). Performing confirmatory antibody testing using adjunct methods improves specificity. Antibody-mediated demyelinating paraneoplastic neuropathies are limited to MAG-IgM (IgM-MGUS, Waldenström's, and myeloma), with the others associated with cytokine elevations (VEGF, IL6) caused by osteosclerotic myeloma, plasmacytoma (POEMS), and rarely angiofollicular lymphoma (Castleman's). Paraneoplastic disorders have clinical overlap with other idiopathic antibody disorders, including IgG4 demyelinating nodopathies (NF155 and Contactin-1). This review summarizes the paraneoplastic neuropathies, including those with peripheral nerve hyperexcitability.
Topics: Humans; Paraneoplastic Polyneuropathy; Multiple Myeloma; Peripheral Nervous System Diseases; Isaacs Syndrome; Autoantibodies; Peripheral Nerves; Immunoglobulin M; Pain
PubMed: 38494281
DOI: 10.1016/B978-0-12-823912-4.00020-7 -
Blood Nov 2023
Topics: Humans; Plasmacytoma; Chromosome Aberrations; Disease Progression
PubMed: 38032673
DOI: 10.1182/blood.2023021859 -
Indian Journal of Otolaryngology and... Dec 2023Solitary extramedullary plasmacytoma (SEP) of the nasal cavity is a rare neoplastic condition characterized by the localized proliferation of abnormal plasma cells. We...
Solitary extramedullary plasmacytoma (SEP) of the nasal cavity is a rare neoplastic condition characterized by the localized proliferation of abnormal plasma cells. We present a case of SEP involving the nasal cavity in a 40-year-old male patient who presented with nasal obstruction and recurrent epistaxis. The diagnosis was confirmed through clinical evaluation, imaging studies, and histopathological examination of excised specimen. The patient underwent trans-nasal endoscopic excision of nasal mass without any adjuvant therapy, which resulted in successful local control. This case report highlights the clinical presentation, diagnostic approach, treatment modalities, and favourable prognosis associated with solitary extramedullary plasmacytoma of the nasal cavity.
PubMed: 37974764
DOI: 10.1007/s12070-023-04061-0 -
Hematology/oncology Clinics of North... Apr 2024Immunocompetent mouse models of multiple myeloma (MM) are particularly needed in the era of T cell redirected therapy to understand drivers of sensitivity and... (Review)
Review
Immunocompetent mouse models of multiple myeloma (MM) are particularly needed in the era of T cell redirected therapy to understand drivers of sensitivity and resistance, optimize responses, and prevent toxicities. Three mouse models have been extensively characterized: the Balb/c plasmacytomas, the 5TMM, and the Vk*MYC. In the last year, additional models have been generated, which, for the first time, capture primary MM initiating events, like MMSET/NSD2 or cyclin D1 dysregulation. However, the long latency needed for tumor development and the lack of transplantable lines limit their utilization. Future studies should focus on modeling hyperdiploid MM.
Topics: Mice; Animals; Humans; Multiple Myeloma; Disease Models, Animal
PubMed: 38233233
DOI: 10.1016/j.hoc.2023.12.014 -
Spine Sep 2023Retrospective analysis.
STUDY DESIGN
Retrospective analysis.
OBJECTIVE
This study aimed to establish nomograms for predicting overall survival (OS) and cancer-specific survival (CSS) in patients with solitary plasmacytoma of the spine (SPS).
SUMMARY OF BACKGROUND DATA
SPS is a rare type of malignant spinal tumor. A systematic study of prognostic factors associated with survival can provide guidance to clinicians and patients. Consideration of other causes of death (OCOD) in CSS will improve clinical practicability.
METHODS
A total of 1078 patients extracted from the SEER database between 2000 and 2018 were analyzed. Patients were grouped into training and testing data sets (7:3). Factors associated with OS and CSS were identified by Cox regression and competing risk regression, respectively, for the establishment of nomograms on a training data set. The testing data set was used for the external validation of the performance of the nomograms using calibration curves, Brier's scores, C-indexes, time-dependent receiver operating characteristic curves, and decision curve analysis (DCA).
RESULTS
Age and grade were identified as factors associated with both OS and CSS, along with marital status, radiation for OS, and chemotherapy for CSS. Heart disease, cerebrovascular disease, and diabetes mellitus were found to be the 3 most common causes of OCOD. The nomograms showed satisfactory agreement on calibration plots for both training and testing data sets. Integrated Brier score, C-index, and overall area under the curve on the testing data set were 0.162/0.717/0.789 and 0.173/0.709/0.756 for OS and CSS, respectively. DCA curves showed a good clinical net benefit. Nomogram-based web tools were developed for clinical application.
CONCLUSION
This study provides evidence for risk factors and prognostication of survival in SPS patients. The novel nomograms and web-based tools we developed demonstrated good performance and might serve as accessory tools for clinical decision-making and SPS management.
LEVEL OF EVIDENCE
3.
Topics: Humans; Plasmacytoma; Nomograms; Retrospective Studies; Bone Neoplasms; Internet; Prognosis
PubMed: 37036328
DOI: 10.1097/BRS.0000000000004679 -
BMC Nephrology Oct 2023Castleman's disease (CD) is a rare disease that has clinical and pathological similarities to lymphoma and is characterized by a high frequency of associated...
BACKGROUND
Castleman's disease (CD) is a rare disease that has clinical and pathological similarities to lymphoma and is characterized by a high frequency of associated immunological dysfunction. ImmunoglobulinG4-related disease (IgG4-RD) is a collection of systemic disorders that affect numerous organs and are also referred to as IgG4-associated sclerosing diseases. CD and IgG4-RD are difficult to separate because they may manifest similar commin clinical features.
CASE PRESENTATION
This case describes a 53-year-old female who, during routine medical check-up, exhibited a progressive increase in serum globulin levels and a simultaneous worsening of anemia symptoms, raising concern for a clonal plasma cell disease such as myeloma. However, bone marrow punctures did not reveal any abnormal plasma cells. Also, serum and urine immunofixation electrophoresis demonstrated no abnormal monoclonal protein bands. In addition, several laboratory findings excluded chronic liver disease, chronic infections caused by bacteria or viruses. Later, we found elevated serum IgG4 levels (10,700 mg/L), and identified multiple enlarged lymph nodes throughout the patient's body. Axillary lymph node aspiration revealed no abnormal lymphocytes, ruling out the possibility of lymphoma. Pathological morphology of the axillary lymph revealed a large number of plasma cells in the lymphatic follicles. In addition, there was a reduction in lymphatic follicle size and apoptosis of the germinal centres. Immunohistochemistry revealed IgG4+/IgG + in > 40% of cells, and more than 100 IgG4 + cells per high powered field (HPF) of specimen. As of now, finding strongly suggested IgG4-RD. This patient was treated with glucocorticoids and various immunosuppressive drugs, such as prednisone, cyclosporine, methotrexate, cyclophosphamide, mycophenolate mofetil, azathioprine and hydroxychloroquine. Unfortunately, the patient did not recover. Ultimately, idiopathic multicentric Castleman disease (iMCD) was diagnosed in relation to the patient's clinical presentation and laboratory tests, and after combination chemotherapy (VCD: Bortezomib, Cyclophosphamide and Dexamethasone), durable remission was achieved without serious adverse effects. During the follow-up period of one year and ten months, the patient remained stable.
CONCLUSION
The diagnosis of Castleman must be distinguished from other disorders such as IgG4-RD, malignant lymphoma, reactive hyperplasia of various lymph nodes (mostly caused by viral infections), plasmacytoma, advanced HIV and rheumatic diseases. Besides observing systemic symptoms, laboratory tests such as immunoglobulin levels, complement levels, interleukin levels, and C-reactive protein levels should also be performed in order to determine a diagnosis.
Topics: Female; Humans; Middle Aged; Castleman Disease; Immunoglobulin G4-Related Disease; Bortezomib; Immunoglobulin G; Cyclophosphamide
PubMed: 37784011
DOI: 10.1186/s12882-023-03335-7 -
Haematologica Dec 2023Multiple Myeloma (MM) is a plasma cell neoplasm originating in the bone marrow and is the second most common blood cancer in the United States. One challenge in...
Multiple Myeloma (MM) is a plasma cell neoplasm originating in the bone marrow and is the second most common blood cancer in the United States. One challenge in understanding the pathogenesis of MM and improving treatment is a lack of immunocompetent mouse models. We previously developed the IL6Myc mouse that generates plasmacytomas at 100% penetrance that phenotypically resemble aggressive MM. Using comprehensive genomic analysis, we found that the IL6Myc tumors resemble aggressive MM by RNA and protein expression. We also found that IL6Myc tumors accumulated fusions and missense mutations in genes that overlap significantly with human myeloma, indicating that the mouse is good model for studying disease etiology. Lastly, we derived cell lines from IL6Myc tumors that express cell surface markers typical of MM and readily engraft into mice, home to the bone marrow, and induce osteolytic disease. The cell lines may be useful in developing immunotherapies directed against BAFF-R and TACI, though not BCMA, and may also be a good model for studying dexamethasone resistance. These data indicate that the IL6Myc model is useful for studying development of aggressive MM and for developing new treatments against such forms of the disease.
Topics: Mice; Humans; Animals; Multiple Myeloma; Bone Marrow
PubMed: 37439384
DOI: 10.3324/haematol.2022.282538 -
Cancers Dec 2023The objective was to review a decade of plasmacytoma (PC) and multiple myeloma (MM) data from French Guiana, and to study its spatial and temporal trends.
BACKGROUND
The objective was to review a decade of plasmacytoma (PC) and multiple myeloma (MM) data from French Guiana, and to study its spatial and temporal trends.
METHODS
This was a retrospective study of MM and PC between January 2005 and December 2014 using cancer registry data, including age-standardized incidence and mortality rates.
RESULTS
There were 110 cases of PC and MM (62 women and 48 men), representing the eighth most frequent malignancy in French Guiana. PC and MM were much more common in females. In men, 79% of cases occurred at ≥55 years, and in women, 90% of cases occurred at ≥50 years. The median age at diagnosis was 60 years for men and 66 years for women, while it was 72 years for men and 75 years for women in mainland France. The incidence rate standardized to the world population was 5.9 patients of PC and MM per 100,000 men/year and 7.8 per 100,000 women/year.
CONCLUSIONS
In our territory, the incidence of PC and MM was higher and patients were diagnosed at a substantially younger age than in mainland France. Women had a greater incidence than men, and there was an increasing temporal trend of incidence among women. African ancestry and the frequency of obesity, notably among women, could have contributed to this observation.
PubMed: 38201605
DOI: 10.3390/cancers16010178 -
Clinical Nuclear Medicine Jun 2024A 56-year-old man with thoracal mass suspected of solitary plasmacytoma was referred for 18 F-FDG PET-CT scan. His PET-CT revealed FDG-avid rib mass and cervical lesion...
A 56-year-old man with thoracal mass suspected of solitary plasmacytoma was referred for 18 F-FDG PET-CT scan. His PET-CT revealed FDG-avid rib mass and cervical lesion at level 2. He also underwent 18 F-fluorocholine (FCH) PET-CT to evaluate possible metastatic spread of the disease. FCH PET-CT showed increased uptake at the rib mass, while the cervical lesion was not FCH-avid. Biopsies confirmed rib lesion was a solitary plasmacytoma; however, the cervical lesion was an amyloid deposited lymph node. This case showed FCH PET-CT is a valuable companion of FDG scan for the evaluation of plasma cell dyscrasias with a better specificity.
Topics: Humans; Male; Middle Aged; Plasmacytoma; Fluorodeoxyglucose F18; Positron Emission Tomography Computed Tomography; Choline; Lymphadenopathy; Amyloid
PubMed: 38557413
DOI: 10.1097/RLU.0000000000005210