Skull base plasmacytoma in young patients aged below 40 years: Radiological perspectives and clinical outcomes.

BACKGROUND: Plasmacytoma of the skull base is a rare manifestation of plasma cell neoplasm with only a few cases documented in literature involving young adults. Plasmacytoma can be an isolated solitary lesion or a secondary manifestation of multiple myeloma (MM). In this study, we report the clinical and radiological characteristics, management, and outcomes of patients under the age of 40 who presented with skull base plasmacytoma and associated neurological manifestations. Additionally, we share our experience in treating a rare case of skull base plasmacytoma diagnosed during pregnancy, in which the patient exhibited a favorable response to myeloma treatment initiated after delivery. CASE SERIES: Four patients were identified, comprising one pregnant female and three male patients, with a median age of 36 years (range 33-37 years). The main presenting symptoms were headache, dizziness, and cranial nerve palsy. All patients received underwent systemic myeloma therapy and radiotherapy with three patients also underwent autologous stem cell transplantation (ASCT). Notably, all patients achieved complete remission. CONCLUSION: Skull base plasmacytoma represents a rare manifestation of plasma cell neoplasms, underscoring the importance of considering it in the differential diagnosis of skull base lesions to ensure early intervention and avoid potential serious complications. Throughout our series, the cornerstone of therapy involved radiotherapy, systemic myeloma therapy, and ASCT, all of which elicited a favorable response in every case.

Isolated Abducens Nerve Palsy: A Rare Manifestation of Recurrent Extramedullary Myeloma.

Multiple myeloma is a plasma cell neoplasm, which may present as a solitary plasmacytoma and, uncommonly, as an extramedullary plasmacytoma. Intracranial plasmacytomas may manifest in central nervous system involvement as cranial nerve palsies. Cranial nerve six palsy is the most common in cases of malignancy. However, isolated abducens palsy presenting as multiple myeloma recurrence is very uncommon. Here, we detail two cases in which intracranial plasmacytoma lesions were present within the region of the Dorello canal, resulting in acute isolated unilateral diplopia from disease recurrence in the absence of systemic marrow involvement.

Cutaneous plasmacytoma with Mott cell differentiation in a dog.

Cytologic evaluation of aspirate slides from a small, <1-cm, interdigital mass on a 9-y-old, spayed female Yorkshire Terrier revealed a proliferation of discrete, round cells containing few-to-many, variably sized, round, eosinophilic, cytoplasmic inclusions. The top differentials based on the cytologic findings were either a plasma cell tumor or a B-cell lymphoma with Mott cell differentiation. The unencapsulated, well-demarcated, multilobulated round-cell neoplasm was completely excised. Immunohistochemical stains were performed to further characterize the neoplasm, which had immunolabeling for multiple myeloma oncogene 1 and vimentin, but did not react with CD3, CD20, melan A, or ionized calcium-binding adapter molecule 1, nor with a Giemsa special stain. Ultrastructurally, the cytoplasmic granules had Russell body-like morphology. A solitary, cutaneous plasmacytoma with Mott cell differentiation has not been described previously in veterinary medicine, to our knowledge.

A Plasmacytoma of the Lateral Pharyngeal Wall: A Diagnostic Enigma.

Plasmacytoma is a rare plasma cell dyscrasia that grows in bones or soft tissues such as the pharynx. Soft tissue plasmacytomas are rare, and a higher burden has been reported in the upper aero-digestive tract, often manifesting as hoarseness, dysphagia, or odynophagia. Due to their rarity, extramedullary plasmacytomas (EMPs) have unknown prognostic factors, and guidelines for optimal management are still lacking. However, radiation therapy and surgery have been used with positive outcomes. Herein, we describe a unique case of plasmacytoma of the pharyngeal tissue in a male patient with a history of HIV disease. The patient completed 28 sessions of radiation therapy, resulting in an improvement in his throat pain and hoarseness. Given the patient's age and lack of traditional risk factors for head and neck cancers, his hoarseness and odynophagia proved to be a diagnostic conundrum. Although infrequent, soft tissue plasmacytomas should be considered in the differential diagnosis of head and neck tumors.

18 F-FDG PET/CT in Solitary Extramedullary Plasmacytoma of the Penis.

ABSTRACT: A 72-year-old man presented with a painless penile mass for 3 months. Contrast-enhanced CT revealed heterogeneous enhancement, whereas 18 F-FDG PET/CT displayed inhomogeneous 18 F-FDG accumulation in the lesion without other abnormal activity. The histopathological examination from biopsied specimen confirmed the diagnosis of a plasmacytoma. However, the subsequent tests, including serum/urine immunofixation electrophoresis, serum/urine free light chain assay, and bone marrow smear/biopsy, did not show any abnormalities. The conclusive diagnosis was a solitary extramedullary plasmacytoma of the penis.

Solitary bone plasmacytoma: Long-term clinical outcomes in a single center.

BACKGROUND: A solitary plasmacytoma is classified into a solitary plasmacytoma of the bone (SBP) and a solitary extramedullary (soft tissue mass) plasmacytoma, based on the site of the lesion. Despite the high local control rate with radiotherapy, approximately half of patients' conditions progress to multiple myeloma (MM) within 3-5 years after diagnosis, with SBP having a worse prognosis. PATIENTS AND METHODS: We retrospectively assessed the treatment and outcomes of patients with SBP in a hospital in China from 2008 to 2021. Twenty-four patients treated over 13 years with SBP were enrolled in this retrospective study. RESULTS: The most common sites for SBP were the axial skeleton and femur. The M protein was detected in 11 patients (46 %), of which 8 (33 %) had light chains, 2 (8 %) had immunoglobulin G kappa and 1 (4 %) had immunoglobulin D kappa. Flow cytometry revealed that 5 patients (21 %) had minimal bone marrow involvement. The treatment included chemotherapy, surgery, and radiotherapy in 18 (75 %), 12 (50 %), and 9 (38 %) patients, respectively, of whom 13 (54 %) received combined treatment. Over a median follow-up period of 67.2 months, 9 patients (38 %) developed MM in a median time of 101.5 months. The 5- and 10-year progression-free survival rates were 67.3 % and 37.4 %, respectively. One patient died due to pneumonia without progression and the other died due to relapse. CONCLUSION: This study confirmed the high rate of progression of SBP to MM, indicating a need for adjunct chemotherapy for the management of SBP.

Plasmacytoma and Amyloid Lymphadenopathy, FDG, and Fluorocholine.

ABSTRACT: 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.

Spontaneous regression of multiple solitary plasmacytoma harboring Epstein-Barr virus: a case report and literature review.

We report a rare case of spontaneous regression (SR) in an elderly untreated patient with multiple solitary plasmacytoma (MSP). Diagnosis of MSP was confirmed through surgical resection of the left nasal cavity mass and subsequent biopsy of the right humerus. The patient was considered ineligible for chemotherapy due to poor performance status. At 3-month post-diagnosis, the patient's condition worsened with deteriorating bone lesions and emergence of a new serum monoclonal protein. However, these clinical findings completely disappeared at 6 months, and positron emission tomography-computed tomography at 1 year confirmed complete metabolic remission. Notably, peripheral blood lymphocyte counts were inversely correlated with tumor progression and remission. Pathological re-evaluation of the initial biopsy specimens revealed programmed cell death protein 1 (PD-1) expression in tumor-infiltrating CD8+ T cells. In addition, tumor cells were infected with Epstein-Barr virus (EBV) but were negative for programmed cell death ligand 1 (PD-L1) expression, which is the most potent immune escape mechanism in tumor cells. While the mechanism underlying SR remains unclear, our findings suggest that host immune response as well as EBV infection may contribute to SR. Further studies are needed to elucidate the clinicopathologic mechanisms of tumor regression in plasma cell neoplasms.

Megalosplenia as an initial manifestation of multiple myeloma with a novel CYLD gene mutation: A case report and literature review.

INTRODUCTION: Megalosplenia in newly diagnosed multiple myeloma (MM) is extremely rare, posing diagnostic and therapeutic challenges due to its unusual location and clinical manifestations and lack of optimal therapeutic strategies. CASE PRESENTATION: A 65-year-old female who was previously healthy presented with a history of ecchymosis on her right leg accompanied by progressive fatigue for 2 weeks. She was admitted to our center in July 2019 due to thrombocytopenia. The patient presented with megalosplenia, anemia, monoclonal protein (λ-light chain type) in the serum and urine, and 45.6% malignant plasma cells in the bone marrow. Splenectomy was performed due to persistent splenomegaly after 3 cycles of the bortezomib plus dexamethasone regimen, and immunohistochemistry results indicated λ-plasmacytoma of the spleen. The same cytogenetic and molecular abnormalities, including t(14;16), 14q32 amplification, 16q32 amplification, 20q12 amplification, and a novel CYLD gene mutation, were identified using fluorescence in situ hybridization and next-generation sequencing in both bone marrow and spleen samples. Therefore, a diagnosis of MM (λ-light chain type, DS III, ISS III, R-ISS III, high-risk) with spleen infiltration was proposed. The patient did not achieve remission after induction treatment with bortezomib plus lenalidomide and dexamethasone or salvage therapy with daratumumab plus ixazomib and dexamethasone. However, she ultimately did achieve very good partial remission with a regimen of bendamustine plus lenalidomide and dexamethasone. Unfortunately, she died of pneumonia associated with chemotherapy. CONCLUSION: To our knowledge, only 8 cases of spleen plasmacytoma at MM diagnosis have been described previously. Extramedullary myeloma patients with spleen involvement at diagnosis are younger and that the condition is usually accompanied by splenic rupture with aggressive clinical features and poor prognosis. Further studies are needed to explore pathogenesis and effective therapies to prolong the survival of such patients.

Detection of circulating normal and tumor plasma cells in newly diagnosed patients of multiple myeloma and their associations with clinical and laboratory parameters.

INTRODUCTION: Circulating plasma cells (CPCs) are frequently noted in variable frequencies in the entire spectrum of plasma cells neoplasms. With advent of high sensitivity multi-parametric flow cytometry, it is not only possible to detect CPCs present in very low numbers, but also to categorise them into circulating tumor plasma cells (CTPCs) and circulating normal plasma cells (CNPCs), based on their marker-profile. This study used multi-colour flow cytometry to evaluate the load of both CTPCs & CNPCs at the time of diagnosis and at six months' time-point of therapy, and evaluated associations of both with clinical and laboratory parameters. METHODS: Twenty one newly diagnosed MM patients were enrolled. Six to nine millilitres of EDTA-anticoagulated peripheral blood sample was used for flow cytometry. A ten colour antibody panel was used for analysis of CPCs, which were categorised further into CTPCs and CNPCs. Approximately 4.8 million events were acquired for the analysis. The percentage &absolute numbers of CTPCs and CNPCs were noted and the proportion of CTPCs out of all CPCs (CTPCs + CNPCs) were also calculated for evaluating their statistical associations. RESULTS: All 21 patients of newly diagnosed MM showed presence of CPCs (CTPCs and/or CNPCs) at the time of diagnosis. The CTPCs were detected in 76 % of the study population. The median percentage and absolute counts of CTPCs were 0.52 % and 54.9 cells /µL, respectively. CNPCs were found in 95 % and the median percentage and absolute counts of CNPCs were 0.025 % and 2.66 cells/µL. After six months of therapy, CPCs (CTPCs and/or CNPCs) were found in all nine patients evaluated for this assay. CTPCs were found 33 %, with a median of 0.075 % and CNPCs were found in 89 % with a median of 0.01 %. Our study showed that the load of CTPCs was found to be higher in patients with presence of lytic bone lesions, plasmacytoma, presence of PCs on peripheral blood film by light microscopy, presence of Chr 1p32 deletion, expression of CD56 and CD81 on CTPCs, and in patients with absence of very good partial response (VGPR). Conversely, the load of CTPCs was significantly lower in patients with concomitant amyloidosis. Also, percentage of bone marrow plasma cells exhibited a significant positive correlation with the absolute count of CTPCs. We observed that the mean percentage of CNPCs was significantly higher in female patients. The load of CNPCs was lower in patients with thrombocytopenia and with hypoalbuminemia. CONCLUSION: Increased burden of CTPCs was associated with presence of lytic lesions, plasmacytomas, Chr 1p32 deletion, expression of CD56 and CD81 on tumor cells and with failure to achieve very good partial response. The CNPCs were lower in patients with thrombocytopenia and with hypoalbuminemia. To best ot our knowledge, this is the first study from India on the relevance of circulating tumor plasma cells and the first study in the world to analyse the associations of circulating normal plasma cells in newly diagnosed patients of multiple myeloma. The study also highlights the utility of multi-parametric flow cytometry in identification and enumeration of circulating plasma cells. MICRO ABSTRACT: Circulating plasma cells indicates poorer outcomes in patients of multiple myeloma. Twenty one newly diagnosed multiple myeloma patients were evaluated by flow cytometry to enumerate and characterise circulating tumor plasma cells (CTPCs) and circulating normal plasma cells (CNPCs). Higher load of CTPCs correlated with known poor prognostic markers and poor response to therapy.

Management and Outcomes of Patients with Refractory Solitary Plasmacytoma after Treatment with Definitive Radiation Therapy.

PURPOSE: Radiation therapy (RT) is the standard treatment for solitary plasmacytoma (SP); however, the optimal management of RT-refractory SPs is unknown. We examined outcomes after early systemic therapy, surgical resection, or observation for patients with RT-refractory disease and assessed the potential impact of treatment selection on disease outcomes. METHODS AND MATERIALS: We retrospectively reviewed patients with SP treated with definitive radiation and evaluated at a single institution with persistent disease on imaging or biopsy. Descriptive statistics were used to characterize patient and disease characteristics and treatment outcomes. RESULTS: Of 102 total SP patients, 17 (17%) were RT-refractory. The median RT dose was 45 Gy, and median follow-up was 71 months from end of RT. Fifteen patients had additional treatment for refractory disease at a median time of 9.5 months after RT, with the following subsequent interventions: surgical resection (n = 4), additional RT (n = 2), systemic therapy without evidence of multiple myeloma (MM; n = 4), systemic therapy for progression to MM (n = 5), and observation (n = 2). Of 4 patients treated with surgical resection, 3 progressed to MM 22 to 43 months after diagnosis. Of 2 patients treated with additional RT, neither responded, and both had pathologic confirmation of residual disease after the second course. Four patients treated with systemic therapy without MM all had complete responses on positron emission tomography and no subsequent MM progression. Eight patients were initially observed after RT for ≥12 months (n = 8) or ≥24 months (n = 6). Of the 2 patients in continued observation, both had stable/unchanged avidity after radiation treatment for 12 and 22 months and ultimately had a slow decrease of disease avidity over multiple years. CONCLUSIONS: Patients with RT-refractory SPs can achieve good local control with alternative therapies, such as surgery or systemic therapy, if needed. Additional RT does not seem to be effective. Given the known high rates of progression from SP to MM, close observation of asymptomatic persistent disease until disease progression is likely sufficient in most cases.

Extramedullary Plasmacytoma of the Retroperitoneum Detected on 18 F-FDG PET/CT.

ABSTRACT: Solitary retroperitoneal extramedullary plasmacytoma is a rare neoplasm. A 67-year-old man presented with abdominal pain and left leg weakness. Abdominal CT revealed a large mass in the left retroperitoneum, which demonstrated increased metabolic activity on subsequent 18 F-FDG PET/CT imaging. Furthermore, the patient's serum protein electrophoresis showed positive M-protein results. Pathological examination of the biopsied specimen confirmed the diagnosis of extramedullary plasmacytoma.

Clinico-pathological profile of patients with plasma cell neoplasms with special reference to bone marrow fibrosis and amyloid deposition.

To clarify the significance of bone marrow fibrosis and amyloid deposition in plasma cell neoplasm, a retrospective cross-sectional study for a period of 3 years was conducted. Patients who underwent bone marrow aspiration and biopsy with suspicion of plasma cell neoplasms were included in the study. The bone marrow findings were correlated with clinical profile of the patient along with biochemical parameters, cytogenetics, Fluorescent in situ hybridization (FISH) wherever available. A total of 273 bone marrow aspirates and biopsies of patients with suspected plasma cell neoplasms were analyzed. There were 181 male patients and 92 female patients (Male: Female = 1.96: 1). There were 245 cases of multiple myeloma (89.7%), 8 cases of primary amyloidosis (2.9%) and 6 monoclonal gammopathy of undetermined significance (MGUS) (2.1%), 5 cases of plasmacytoma (1.8%) and 4 cases of smouldering myeloma (1.4%), 5 cases of POEMS syndrome (1.8%). Bone marrow fibrosis was noted in 12 patients at diagnosis (4.3%). Among the parameters studied, only the mean Hemoglobin was significantly low in patients with marrow fibrosis. Amyloid deposition in various organs including bone marrow, kidney, liver etc., were noted in 17 patients overall (6.2%). In conclusion, the incidence of fibrosis (4.3%) and amyloidosis (6.2%) associated with plasma cell neoplasms were much lower in our study as compared to published studies.

Myocardial plasma cell tumor with intratumoral amyloidosis in a dog.

A 12-year-old mixed breed dog was evaluated for marked hypercalcemia that was identified during assessment for acute polydipsia and polyuria. Physical examination identified a new grade II/VI left apical systolic murmur. A mass involving the left ventricular posterior wall and left atrium was identified by echocardiography, suggesting neoplastic invasion into the myocardium. The patient was euthanized, and post-mortem cardiac evaluation identified an intramyocardial amyloid-producing plasma cell tumor. Multiple myeloma was suspected but could not be confirmed due to the limited post-mortem evaluation. This case is the first report of myocardial amyloidosis in a dog with a myeloma-related disorder (MRD). Dogs with MRD and myocardial involvement may not exhibit clinical signs that localize to the cardiovascular system; therefore, echocardiography should be considered during the staging process.

FDG PET/CT Image of Extramedullary Plasmacytoma in the Anterior Mediastinum.

ABSTRACT: Extramedullary plasmacytoma in the anterior mediastinum is very rare. We report FDG PET/CT findings of anterior mediastinum extramedullary plasmacytoma in a 54-year-old woman. On FDG PET/CT, it presented as a solitary anterior mediastinum mass with increased FDG uptake. The final pathology supported a diagnosis of extramedullary plasmacytoma. This case hints us that extramedullary plasmacytoma should be regarded as a differential diagnosis when we encounter a solitary anterior mediastinum mass with intense FDG uptake.

Rapidly Enlarging Parotid Mass in a Person Living with HIV: A Case of Multiple Myeloma with Extramedullary Plasmacytoma.

BACKGROUND The differential diagnosis for a parotid mass is broad, including infectious, autoimmune, and neoplastic etiologies. In people with HIV, regardless of viral suppression or immune status, neoplastic causes are more common. This report describes the evaluation of a woman with a large parotid mass, with an ultimate diagnosis of multiple myeloma with extramedullary plasmacytoma. CASE REPORT A 51-year-old woman with HIV infection presented with headache, weight loss, and right facial mass that was present for 5 years but more rapidly enlarging in the prior year. CD4 count was 234 cells/mL, and HIV RNA was 10 810 copies/mL. Physical examination was significant for a large deforming right-sided facial mass, decreased sensation in the V1 and V2 distributions, and right-sided ophthalmoplegia and ptosis. MRI and PET/CT scan confirmed a metabolically active large parotid mass with extension into the cavernous sinus. An IgG kappa monoclonal spike was present on serum protein electrophoresis. Incisional biopsy of the facial mass showed atypical lymphoid cells with plasmablastic and plasmacytic morphology with a high mitotic rate and proliferation index. She was diagnosed with R-ISS stage II IgG kappa multiple myeloma with extramedullary plasmacytoma, and initiated on chemotherapy, radiation, and antiretroviral therapy. CONCLUSIONS A rapidly enlarging parotid mass should prompt timely evaluation and biopsy for definitive diagnosis, particularly in immunocompromised patients, including people with HIV. Extramedullary plasmacytomas have a more aggressive disease process in people with HIV and are associated with high-risk multiple myeloma and progression, as seen in this patient.

MUM1/IRF4 immunolabeling of neoplastic Langerhans histiocytes in a putative case of canine Langerhans cell histiocytosis.

Langerhans cell histiocytosis is a systemic histiocytic proliferative disease with cutaneous manifestations which is well described in human medical literature and has relatively recently been reclassified as a neoplastic disorder. The diagnosis of canine Langerhans cell histiocytosis has been proposed in the veterinary literature to refer to a histiocytic proliferative disease in the dog with clinical and histopathologic features that mirror the human disease. However, reports that invoke this diagnosis are rare and often lack complete diagnostic characterization. This case report presents an extensive diagnostic investigation of a putative case of Langerhans cell histiocytosis in a 3-year-old male castrated Golden Retriever dog, including gross, cytologic, histopathologic, and immunohistochemical findings. Furthermore, we document that canine LCH may have positive immunolabeling for the transcription factor multiple myeloma oncogene 1/interferon regulatory factor 4 (MUM1/IRF4), which is classically used for the diagnosis of canine plasma cell neoplasms.