Monoclonal Gammopathy of Undetermined Significance: A Comprehensive Review.

Monoclonal Gammopathy of Undetermined Significance (MGUS) is an asymptomatic premalignant plasma cell dyscrasia with a predominate rise of the IgG immunoglobulin fraction without end-organ damage, often diagnosed incidentally. Despite its progression into various subsequent forms of hematological malignancies, MGUS remains underdiagnosed. A literature search was conducted using the Medline, Cochrane, Embase, and Google Scholar databases, including articles published until December 2022. Keywords used encompassed "Monoclonal Gammopathy of Undetermined Significance," "Plasma Cell dyscrasia," "Monoclonal gammopathy of renal significance," and "IgM Monoclonal gammopathy of Undetermined Significance," This study aimed to conduct a critical review to update knowledge regarding the pathophysiology, risk factors, clinical features, diagnostic protocols, complications, and current and novel treatments for MGUS. We recommend a multidisciplinary approach to manage MGUS due to the complexity of the illness's etiology, diagnosis, and therapy. This comprehensive review also highlights future prospects, such as developing screening protocols for at-risk populations, prevention of disease progression by early diagnosis through genome-wide association studies, and management using Daratumumab and NSAIDs.

A 65-Year-Old Man With Weight Loss, Peripheral Neuropathy, and Lower Extremity Swelling.

CASE PRESENTATION: A 65-year-old man with no past medical history sought treatment at the hospital with lower extremity swelling, pain, tingling in a stocking-glove distribution, and syncope. He reported a 23-pound unintentional weight loss. He felt unsteady walking with a couple of falls, and his exercise tolerance was limited to several hundred feet. He did not report vision changes, dysphagia, bowel or bladder problems, tremor, orthopnea, lightheadedness, or chest pain. He did not report any history of substance misuse, high-risk sexual behavior, or concerning exposures. The patient was admitted for further workup.

Síndrome de hiperviscosidade em paciente com mieloma múltiplo / Hyperviscosity syndrome in multiple myeloma patients

O mieloma múltiplo é uma neoplasia progressiva e incurável de células B, caracterizado pela proliferação desregulada e clonal de plasmócitos na medula óssea. A síndrome de hiperviscosidade é uma das complicações relacionadas às gamopatias monoclonais, sendo considerada emergência oncológica. O objetivo deste estudo foi descrever o quadro clínico de um paciente diagnosticado com mieloma múltiplo que apresentou síndrome de hiperviscosidade, avaliando a prevalência de sinais e sintomas, bem como características fisiopatológicas dessa entidade clínica. Foi revisado o prontuário de um paciente internado na enfermaria da Clínica Médica do Hospital Regional do Cariri (CE) no período de junho a julho de 2018. Além disso, foi realizada revisão de literatura em base de dados (PubMed®) direcionada ao tema proposto. O diagnóstico de mieloma múltiplo foi comprovado por mielograma, sendo prontamente iniciada a corticoterapia e avaliada a resposta clínica após essa terapêutica. Apesar de incomum e menos frequentemente relacionada ao mieloma múltiplo, a síndrome de hiperviscosidade está relacionada a uma grande taxa de mortalidade quando apresenta diagnóstico tardio. A terapia de primeira linha indicada para a síndrome de hiperviscosidade foi a plasmaferese, no entanto, as condições clínicas (instabilidade hemodinâmica) impossibilitaram sua realização. O desfecho deste caso foi o óbito do paciente. Concluiu-se que o diagnóstico precoce e a intervenção terapêutica estão diretamente relacionados à ocorrência de menor incidência de complicações relacionadas ao mieloma múltiplo e à síndrome de hiperviscosidade.

Multiple myeloma is a progressive and incurable B-cell neoplasm characterized by unregulated and clonal proliferation of plasmocytes in the bone marrow. Hyperviscosity syndrome is one of the complications related to monoclonal gammopathies and is considered an oncological emergency. The aim of this study was to describe the clinical condition of a patient diagnosed with multiple myeloma who presented hyperviscosity syndrome, evaluating the prevalence of symptoms and signs, as well as the pathophysiological characteristics of this clinical entity. The medical records of a patient admitted to the Internal Medicine ward of the Hospital Regional do Cariri (CE) from June to July of 2018 were reviewed. In addition, we conducted a literature review in a database (PubMed®) directed to the theme proposed. The diagnosis of multiple myeloma was confirmed by myelogram, and corticosteroid therapy was promptly initiated and the clinical response was evaluated after this therapy. Although uncommon and less frequently related to multiple myeoloma, hyperviscosity syndrome is related to a high mortality rate when diagnosed late. The first line therapy indicated to hyperviscosity syndrome was plasmapheresis; however, the clinical conditions (hemodynamic instability) precluded its performance. The outcome of this case was the patient's death. Thus, it was concluded that early diagnosis and therapeutic intervention are directly related to the occurrence of lower incidence of complications related to multiple myeloma and hyperviscosity syndrome.

Epstein - Barr virus association with plasma cell neoplasms.

AIMS: Epstein-Barr virus (EBV) expression has been reported in several hematopoietic and non-hematopoietic disorders but its expression in plasma cell neoplasms has been largely limited to immunodeficiency-related cases such as in the setting of post-organ transplantation or human immunodeficiency virus (HIV) infection. The aim of this study is to evaluate the association of EBV with plasma cell neoplasms, mainly in immunocompetent patients. METHODS AND RESULTS: We retrospectively studied 147 cases of patients with different plasma cell neoplasms (109 plasma cell myelomas, 22 plasmacytomas, and 16 monoclonal gammopathy cases). Six patients were immunocompromised. EBV was positive in 6 cases; 3 immunocompromised (2 patients with HIV infection and 1 patient was post-renal transplant) and 3 immunocompetent patients with plasmacytoma and variable plasmablastic features. CONCLUSIONS: Our data shows that EBV was negative in all plasma cell myeloma cases in immunocompetent patients and has an overall low association with the different plasma cell neoplasms in the immunocompetent setting. When expressed, it is usually associated with variable plasmablastic features.

TEMPI Syndrome: Erythrocytosis in Plasma Cell Dyscrasia.

TEMPI (telangiectasias, erythrocytosis with elevated erythropoietin, monoclonal gammopathy, perinephric fluid collections, intrapulmonary shunting) syndrome is a newly described clinical entity that is generally considered a plasma cell dyscrasia with multiple system involvement. The etiology and pathophysiology of this condition remains elusive. Nevertheless, clonal plasma cells and monoclonal protein appear to be major contributors. The early diagnosis of TEMPI syndrome is essential because therapies targeting the underlying plasma cells can lead to a dramatic response. Bortezomib-based chemotherapy, daratumumab monotherapy, and autologous hematopoietic stem cell transplantation can result in reversal of most manifestations. Nevertheless, the diagnosis of TEMPI syndrome remains a substantial challenge owing to its rarity and the complexity of clinical presentations. TEMPI syndrome is often misdiagnosed as other causes of erythrocytosis, resulting in a delayed diagnosis and further clinical deterioration. The aim of the present review was to present the clinical and biologic features of TEMPI syndrome, highlighting the differential diagnosis and outlining the present understanding of its pathophysiology and treatment.

Plasma cell neoplasm as a risk factor for early thrombosis of arteriovenous fistula.

INTRODUCTION: We hypothesized that presence of plasma cell neoplasms might be a risk for thrombosis of arteriovenous fistulas (AVFs) as well as other well-known factors including age, sex, race, and presence of diabetes mellitus or certain vascular disorders. METHODS: In this single-center, retrospective study based on medical record data, we investigated the influence of plasma cell neoplasms and the above-mentioned factors on the occurrence of complete occlusive thrombosis of the AVF within 30 days after surgery for creation of the AVF. Thrombosis was defined as the absence of bruit or thrill on auscultation and palpation, throughout systole and diastole. FINDINGS: We retrospectively assessed the medical records of 91 patients with end-stage renal failure, including 8 patients with plasma cell neoplasm (5 with multiple myeloma and 3 with amyloid light-chain amyloidosis), who underwent surgical creation of an AVF at the wrist or anatomical snuff box for the first time between April 2014 and December 2016. Early thrombosis (i.e., within 30 days of surgery) occurred in 50.0% (4/8) and 10.8% (9/83) of patients with and without plasma cell neoplasm, respectively (P = 0.013). Multivariate analysis revealed that, after adjusting for baseline characteristics, plasma cell neoplasm was the only significant risk factor for early AVF thrombosis (odds ratio, 38.8; 95% confidence interval, 4.0-378.9; P = 0.0017). DISCUSSION: Considering the poor prognosis of plasma cell neoplasm and its association with higher risk for AVF thrombosis, another type of vascular access is likely to be more suitable than AVF in such patients.

Concomitant Occurrence of Blastic Plasmacytoid Dendritic Cell Neoplasm and Acute Myeloid Leukaemia after Lenalidomide Treatment for.

BACKGROUND: Myelodysplastic syndromes with chromosome 5 long arm deletion (5q-mds) may benefit from lenalidomide treatment. However, unresponsive patients have a high risk for clonal evolution and progression to acute myeloid leukemia. Case: We describe a 5q-patient treated with lenalidomide, who concomitantly developed acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm, a rare and highly aggressive lymphoma. CONCLUSIONS: Evolution of 5q- syndrome to acute myeloid leukemia and blastic plasmacytoid dendritic cell neoplasm may have occurred through various mechanisms, including persistence of neoplastic lenalidomide-resistant stem cells and selection of a more aggressive clone via lenalidomide augmentation of the ARPC1B gene, or because of lenalidomide stimulation on dendritic cells. Further studies are needed to clarify lenalidomide oncogenic potential.

Two cases of feline paraneoplastic alopecia associated with a neuroendocrine pancreatic neoplasia and a hepatosplenic plasma cell tumour.

BACKGROUND: Feline paraneoplastic alopecia (FPA) is a rare condition listed among the cutaneous paraneoplastic syndromes, which occurs in association with pancreatic carcinoma, cholangiocarcinoma, hepatocellular carcinoma and metastatic intestinal carcinoma. OBJECTIVES: To describe the clinicopathological findings of paraneoplastic alopecia in two cats each with an uncommon tumour not previously reported in association with FPA. ANIMALS: Paraneoplastic alopecia was associated with neuroendocrine pancreatic neoplasia in a Persian cat and with a hepatosplenic plasma cell tumour in a domestic short hair cat. RESULTS: FPA was suspected based on age, rapid onset of clinical signs, ventral distribution of alopecia, shiny appearance of the skin and telogenization/miniaturization of the follicles on histopathology. The nature of the tumours was determined through cytology, postmortem, histopathological and immunohistochemical examination, and capillary immunoelectrophoresis. A causative association between the skin lesions and the tumour was suggested by clinical and histopathological features shared with previously published cases. CONCLUSIONS AND CLINICAL IMPORTANCE: Pancreatic neuroendocrine and plasma cell tumour should be considered as differential diagnoses when evaluating FPA.

Crystal-storing histiocytosis: a clinicopathological study of 13 cases.

AIMS: Crystal-storing histiocytosis (CSH) is a rare lesion composed of histiocytes with abnormal intralysosomal accumulation of immunoglobulin (Ig) as crystals, reported in patients with plasmacytic/lymphoplasmacytic neoplasms. The aims of this study were to report the clinicopathological features of 13 patients with CSH, and to describe the proteomic composition of the crystals in three cases analysed by mass spectrometry (MS). METHODS AND RESULTS: There were seven men and six women, with a median age of 60 years (range, 33-79 years). CSH was generalized in one patient (8%) and localized in 12 (92%) patients, involving various sites. CSH was associated with a low-grade B-cell lymphoma with plasmacytoid differentiation or a plasma cell neoplasm in all cases. In 10 (77%) cases, CSH represented >50% of the neoplastic infiltrate. According to immunohistochemical studies, histiocytes were positive for monotypic kappa in 5 (50%) cases, and for monotypic lambda in 4 (40%) cases; in 1 (10%) case, the results were equivocal. MS analysis of the histiocyte contents in all three tested cases showed a predominance of variable-region fragments of Ig light and/or heavy chains. CONCLUSIONS: CSH is frequently associated with an underlying lymphoplasmacytic neoplasm. MS findings suggest that Ig alterations and/or possibly defects in the ability of histiocytes to process Ig play a role in pathogenesis.

Co-existent B-cell and plasma cell neoplasms: a case series providing novel clinical insight.

Concomitant plasma cell (PCN) and B-cell neoplasms (BCN) in a single patient have been infrequently reported. This study reviewed nine such patients at the institution - six had multiple myeloma (MM) associated with a BCN (MM/B group) and three had AL amyloidosis (ALA) with a BCN (ALA/B group). This study describes two syndromes of MM/B - three patients presented with CLL and subsequently developed MM, while three presented with MM and monoclonal B-cell lymphocytosis. In the ALA/B group, all three patients had systemic ALA and a BCN. Responses of the BCN and PCN to treatment correlated. In the two patients whose MM relapsed, the BCN simultaneously relapsed. The finding that the BCN may relapse in tandem with the MM argues against a coincidental relationship between the two.

Plasmablastic lymphoma of the anal canal in an HIV-infected patient.

BACKGROUND: The advent of antiretroviral therapy increased the life expectancy of human immunodeficiency virus (HIV)-positive patients and, consequently, the morbidity and mortality due to neoplasms. Plasmablastic lymphoma is one such neoplasm that generally presents with involvement of the oral cavity; cases of extra-oral involvement are rare. CASE REPORT: We report a case of plasmablastic lymphoma in a 46-year-old woman for whom the initial clinical manifestation was a painless perineal tumor accompanied by fecal incontinence. CONCLUSIONS: The possibility of this neoplasm should be considered in patients with HIV/acquired immune deficiency syndrome (HIV/AIDS) because its early diagnosis is essential so that the start of the treatment is not delayed.

[Clinical features of peripheral neuropathy in paraproteinemic hemoblastosis].

OBJECTIVE: Peripheral neuropathy often occurs as a side effect of medication or as a manifestation of system disease. The purpose of this study was to evaluate the features of polyneuropathy with verified paraproteinemic hemoblastosis. MATERIAL AND METHODS: We studied 104 patients, 72 women 32 men, aged 24-79 years. Along with neurological examination, authors studied vibration sensitivity and used electromyography and several scales for assessment of pain syndrome and other clinical presentations. RESULTS AND СONCLUSION: Clinical variants of peripheral neuropathy - neuropathy associated with paraproteinemia and neuropathy during treatment of advanced multiple myeloma with bortezomib (bortezomib-induced neuropathy), were singled out. An algorithm for the examination and treatment of patients with peripheral neuropathy was proposed.

Primary cerebral low-grade B-cell lymphoma, monoclonal immunoglobulin deposition disease, cerebral light chain deposition disease and "aggregoma": an update on classification and diagnosis.

BACKGROUND: This work aims to add evidence and provide an update on the classification and diagnosis of monoclonal immunoglobulin deposition disease (MIDD) and primary central nervous system low-grade lymphomas. MIDD is characterized by the deposition of light and heavy chain proteins. Depending on the spatial arrangement of the secreted proteins, light chain-derived amyloidosis (AL) can be distinguished from non-amyloid light chain deposition disease (LCDD). We present a case of an extremely rare tumoral presentation of LCDD (aggregoma) and review the 3 previously published LCDD cases and discuss their presentation with respect to AL. CASE PRESENTATION: A 61-year-old woman presented with a 3½-year history of neurologic symptoms due to a progressive white matter lesion of the left subcortical parieto-insular lobe and basal ganglia. 2 former stereotactic biopsies conducted at different hospitals revealed no evidence of malignancy or inflammation; thus, no therapy had been initiated. After performing physiological and functional magnetic resonance imaging (MRI), the tumor was removed under intraoperative monitoring at our department. Histological analysis revealed large amorphous deposits and small islands of lymphoid cells. CONCLUSION: LCCD is a very rare and obscure manifestation of primary central nervous system low-grade lymphomas that can be easily misdiagnosed by stereotactic biopsy sampling. If stereotactic biopsy does not reveal a definite result, a "wait-and-see" strategy can delay possible therapy for this disease. The impact of surgical removal, radiotherapy and chemotherapy in LCDD obviously remains controversial because of the low number of relevant cases.

Post-transplant lymphoproliferative disease of donor origin, following haematopoietic stem cell transplantation in a patient with blastic plasmacytoid dendritic cell neoplasm.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an extremely rare condition that originates from dendritic cells. We report on the first case of Epstein-Barr virus (EBV)-driven post-transplant lymphoproliferative disorder (PTLD) of donor origin in a BPDC patient post-allogeneic haematopoietic stem cell transplantation (HSCT). Flow cytometry study identified a cell population CD4+/CD56+/CD45RA+/CD123+/TCL1+ suggestive of BPDCN diagnosis, which was confirmed by a lymph node biopsy (cells positive for BCL11a, BDCA-2, CD2AP, CD123, TCL1 and S100). Cytogenetic analysis revealed a complex karyotype: (19 metaphase) 47,XX,t(1;6)(q21;q2?5),-13 + 2mar[11]/47, XX, +21 [3]/46,XX [5]. The patient was started on acute myeloid leukaemia (AML) induction schedule, and subsequently an allogeneic HSCT was performed. On day +36 post-HSCT, bone marrow biopsy/aspirate showed complete morphological remission, and chimerism study showed 100% donor chimera. However, on day +37, the patient was found to have enlarged cervical and supraclavicular lymphoadenopathy, splenomegaly and raised lactic dehydrogenase. EBV-DNA copies in blood were elevated, consistent with a lytic cycle. A lymph node biopsy showed EBV encoded RNA and large atypical B cells (CD45dim-, CD4+/CD56+, monoclonal for k-chain, CD19+/CD20+/CD21+/CD22+/CD38+/CD43+/CD79ß-/CD5-/CD10-), consistent with PTLD monomorphic type. Chimerism study showed that PTLD was of donor origin. This case together with the recent literature findings on BPDCN and PTLD are discussed.

Plasmablastic lymphoma of the retroperitoneum in an HIV- and HCV-positive patient: hard to diagnose and harder to treat.

Plasmablastic lymphoma (PBL) is an aggressive diffuse large B-cell lymphoma (DLBCL) with plasmablastic features that was initially described in the oral cavity of HIV-infected individuals. PBL remains a diagnostic challenge given its close morphologic resemblance and overlapping immunophenotypic patterns to other B-cell lymphoid malignancies and plasmablastic plasma cell myeloma (PCM) with extramedullary involvement. The presence of serum monoclonal protein and radiographic evidence of lytic bone lesions favors the diagnosis of plasma cell myeloma over PBL. Distinguishing PBL from PCM is important as PBL is treated with a completely different chemotherapy regimen compared to PCM. PBL carries a guarded prognostic profile among DLBCLs with high relapse rate and poor median survival. We present a case of a 44-year-old HIV-positive man who presented with a large retroperitoneal mass associated with obstructive uropathy, sacral radiculopathy, and inferior vena caval compression. The mass was initially mistaken to be a PCM on histopathology; however, subsequent investigations revealed an extra-oral PBL with plasmacytic differentiation. To our knowledge, this will be the first case of PBL of the retroperitoneum in an HIV- and HCV-positive patient and the second one at this location in the English-language literature. In this report, key differentiating points between PBL versus PCM and newer therapeutic agents such as proteasome inhibitors have been discussed along with related review of literature.