Extramedullary Plasmacytoma of the Penis as a First Manifestation of Multiple Myeloma: A Case Report.

INTRODUCTION: Plasmacytoma is a rare plasma-cell neoplasm, which includes bone and extramedullary types. While most cases occur in the head and neck, our report presents an unusual case of extramedullary plasmacytoma (EMP) in the penis, emphasizing the diverse locations of this condition. CASE PRESENTATION: An 88-year-old man, post-hydrocelectomy, presented with a palpable penile mass causing urinary symptoms. CT scans revealed a tumor with extracapsular spread and potential urethral involvement. Biopsy confirmed lymphoma, later identified as extramedullary plasmacytoma. A follow-up whole-body CT scan was performed, revealing multiple areas of bone rarefaction of the dens of the axis. His diagnosis has been further specified as multiple myeloma. Treatment with lenalidomide, bortezomib, and dexamethasone led to significant penile tumor reduction and improved voiding symptoms after three cycles. CONCLUSION: A rare case of primary EMP in the penis is reported, with only two documented cases of EMP in this location. The etiology of EMP remains unclear, possibly linked to chronic infection, irritation, or inflammation. EMP typically occurs in soft tissues, commonly in the head and neck, presenting as submucosal masses with symptoms in individuals aged 50-70. Diagnosis requires demonstrating monoclonal plasma cell infiltration and excluding multiple myeloma. While EMPs are often treated with radiotherapy, a patient with bone rarefaction suggestive of multiple myeloma requires first-line chemotherapy. This case highlights the importance of recognizing myeloma-defining events for appropriate treatment.

Primary central nervous system other iatrogenic immunodeficiency-associated lymphoproliferative disorders presenting as extraosseous plasmacytoma with a progressive clinical course: A case report and literature review.

Other iatrogenic immunosuppressive-associated lymphoproliferative disorders (OIIA-LPDs) rarely occur in the central nervous system (CNS). Additionally, they almost always present as lymphoma and withdrawal by cessation of immunosuppressive treatment. We report a case of primary CNS OIIA-LPD that presented as extraosseous plasmacytoma (EP) with a progressive clinical course in spite of immunosuppressive treatment cessation. A 78-year-old man with a history of rheumatoid arthritis (RA) presented with a month-long headache. Magnetic resonance imaging showed mass lesions in the left temporal lobe, left middle fossa, and intradural cervical spine. The left temporal lesion was resected and diagnosed as EP histologically, and OIIA-LPD presented as plasmacytoma integrally due to his history of immunosuppressive treatment using tacrolimus for RA. Despite immunosuppressive treatment cessation, OIIA-LPD lesions did not regress but, on the contrary, showed a progressive clinical course. Considering his advanced age and renal dysfunction, postoperative treatment with radiation and moderate chemotherapy using prednisolone were administrated. Subsequently, the disease state stabilized, and the patient had a Karnofsky performance status score of 90 for 6 months; however, the tumor recurred with meningeal dissemination, and he died 8 months after treatment. Types of OIIA-LPD onset as EP and its progressive clinical course resistant to cessation of immunosuppressive treatment are rare. Moreover, this OIIA-LPD disease state worsened despite its radiosensitivity. We believe the progressive clinical course of this OIIA-LPD case with its high cell proliferation is similar to Epstein-Barr virus negative plasmablastic lymphoma, which could lead to a poor outcome.

[Effect of autologous hematopoietic stem cell transplantation on minimal residual disease in patients with multiple myeloma].

Objective: To evaluate the effect of autologous hematopoietic stem cell transplantation (ASCT) on minimal residual disease (MRD) in patients with multiple myeloma (MM). Method: From August 2018 to August 2021, 92 patients newly diagnosed with MM who had received either the bortezomib combined with cyclophosphamide and dexamethasone (VCD) or the bortezomib, lenalidomide and dexamethasone (VRD) induction regimens followed by sequential ASCT were assessed for overall survival (OS) and the MRD negative rate. The differences in efficacy at 100 days after transplantation were assessed according to factors, including age, risk stratification, target organ damage, and pre-transplant regimen, etc. Results: Among the 92 patients, there were 45 males and 47 females, with a median age of 57.3 (35-67) years. Fifty-seven patients received the VCD regimen, and 35 received VRD as induction regimen. Forty-three patients received busulphan combined with cyclophosphamide and etoposide (BCV), and 49 patients received high-dose melphan (HDM) regimen as pre-transplantation treatment. After transplantation, the total complete remission (CR) rate of 92 patients increased from 23.9% (22/92) to 58.7% (54/92), and the MRD negative rate increased from 4.4% (4/92) to 33.7% (31/92), and the differences were statistically significant (all P<0.05). After transplantation, the MRD negative rates of patients with PR, VGPR and ≥CR before transplantation were 17.6% (6/34), 33.3% (12/36) and 59.1% (13/22), respectively (P=0.006). The CR rates of patients with or without plasmacytoma at initial diagnosis were 36.4% (4/11) and 65.4% (53/81), respectively (P=0.029), and the MRD negative rates were 18.2% (2/11) and 39.5% (32/81), respectively (P=0.037), and the differences were statistically significant. The MRD negative rates in high-risk patients and standard-risk group were 30.5% (12/28) and 42.9% (18/59), respectively (P=0.258). For patients who achieved efficacy above VGPR before transplantation, the MRD negative rates after transplantation in VCD-induced group and VRD group were 29% (9/31) and 59.3% (16/27), respectively (P=0.033), and in BCV group and HDM group were 24% (6/25) and 57.6% (19/33), respectively (P=0.016), the differences between the groups were both statistically significant. Conclusion: ASCT can overcome the adverse factors such as high-risk cytogenetic abnormalities, and significantly improve the CR rate and MRD negative rate of MM patients. However, the benefit for patients with plasmacytoma at initial diagnosis is not as good as that of patients without.

Successful treatment with pomalidomide and intrathecal injections for central nervous system plasmacytoma in a patient under haemodialysis.

WHAT IS KNOWN AND OBJECTIVES: The involvement of the central nervous system (CNS) in multiple myeloma (MM) is uncommon and has an extremely poor prognosis, and optimal treatment strategies for the CNS MM patients have not yet been established. CASE SUMMARY: A 71-year-old MM patient with severe renal impairment exhibited extramedullary relapse in the CNS and progression while being treated with lenalidomide and dexamethasone. However, she achieved very good partial remission after a treatment with pomalidomide, cyclophosphamide and dexamethasone (PCD) in combination with intrathecal chemotherapy. WHAT IS NEW AND CONCLUSION: This is the first case report to describe MM with CNS involvement in a patient who had responded to PCD under haemodialysis. The combined intrathecal administration of cytotoxic agents and PCD may prolong survival and is tolerated well by patients with severe renal impairment.

Pomalidomide-dexamethasone for treatment of soft-tissue plasmacytomas in patients with relapsed / refractory multiple myeloma.

OBJECTIVE: The presence of plasmacytomas (Ps) in patients with multiple myeloma (MM) is associated with a poor outcome, both in patients treated conventionally and in patients treated with novel agents. Two types of plasmacytomas have being recognized: paraskeletal plasmacytomas (PPs) and extramedullary plasmacytomas (EMPs), being the incidence of EMPs lower but with worse prognosis. Our aim has been to analyze the efficacy of the pomalidomide-dexamethasone combination in this patient profile. METHOD: In the present study, the efficacy of pomalidomide and dexamethasone in 21 patients from nine hospitals of Catalonia (Spain), with relapsed or refractory MM and Ps, was analyzed. For this purpose, we describe the evolution of paraprotein in serum and urine and the size of plasmacytomas during treatment with pomalidomide-dexamethasone. RESULTS: While 34% of the patients achieved a paraprotein response, only two patients with PPs (9%) responded (RC and PR). There were no responses among patients with EMPs. The median progression-free survival from the start of treatment with pomalidomide/dexamethasone was only 1.7 months and the median overall survival of 4.5 months. CONCLUSION: In conclusion, pomalidomide and dexamethasone has limited efficacy in patients with advanced MM and soft-tissue plasmacytomas.

Hematogenous extramedullary relapse in multiple myeloma - a multicenter retrospective study in 127 patients.

The current study assesses the characteristics and outcomes of multiple myeloma (MM) patients, treated with novel agents for hematogenous extramedullary (HEMM) relapse. Consecutive patients diagnosed with HEMM between 2010-2018 were included. Patients' characteristics at diagnosis and at HEMM presentation, response to treatment, survival and factors predicting survival were recorded and analyzed. A group of 127 patients, all diagnosed with HEMM by imaging (87.3%) and/or biopsy (79%), were included. Of those, 44% were initially diagnosed with ISS3, 57% presented with plasmacytomas, and 30% had high-risk cytogenetics. Median time to HEMM was 32 months. In multivariate analysis, ISS3 and bone plasmacytoma predicted shorter time to HEMM (P = .005 and P = .008, respectively). Upfront autograft was associated with longer time to HEMM (P = .002). At HEMM, 32% of patients had no BM plasmacytosis, 20% had non-secretory disease and 43% had light-chain disease. Multiple HEMM sites were reported in 52% of patients, mostly involving soft tissue, skin (29%), and pleura/lung (25%). First treatment for HEMM included proteasome inhibitors (50%), immunomodulatory drugs (IMiDs) (39%), monoclonal antibodies (10%), and chemotherapy (53%). Overall response rate (ORR) was 57%. IMiDs were associated with higher ORR (HR 2.2, 95% CI 1.02-4.7, P = .04). Median survival from HEMM was 6 months (CI 95% 4.8-7.2). Failure to achieve ≥VGPR was the only significant factor for worse OS in multivariate analyses (HR = 9.87, CI 95% 2.35 - 39, P = .001). In conclusion, HEMM occurs within 3 years of initial myeloma diagnosis and is associated with dismal outcome. The IMiDs might provide a higher response rate, and achievement of ≥VGPR predicts longer survival.

Five cases of orbital extramedullary plasmacytoma: diagnosis and management of an aggressive malignancy.

Purpose: Multiple myeloma is an insidious haematological malignancy characterised by monoclonal proliferation of plasma cells in the bone marrow. Extramedullary plasmacytoma is a rare manifestation of multiple myeloma and usually occurs in the upper respiratory tract. Orbital involvement is particularly uncommon, but may be associated with devastating visual impairment and poor clinical outcomes. Therefore, this article aims to highlight the need for multidisciplinary management of orbital extramedullary plasmacytoma. Methods: This is a retrospective observational case series of five patients. All presented to the authors for management of orbital extramedullary plasmacytomas from 2004 to 2015 at Prince of Wales and Mater Hospitals in Sydney, Australia. Medical records were reviewed for pertinent information including demographics, disease features, management strategy, and clinical progress. The study met Medical Ethics Board standards and is in accordance with the Helsinki Agreements. Results: This case series of five patients underscores the poor prognosis of orbital extramedullary plasmacytoma. Despite aggressive multidisciplinary management, four of these five patients succumbed to their illness during the study period. However, multidisciplinary management did manage to minimise symptoms and preserve quality of life. Conclusions: On a case-by-case basis, patients may derive palliative benefit from orbital surgery in conjunction with radiotherapy and chemotherapy. Orbital surgeons are encouraged to work within a multidisciplinary framework of medical specialists, including haematologists and radiation oncologists, when determining the optimal management plan in cases of orbital extramedullary plasmacytoma.

Clinical Course of a Patient With Kidney Failure Due to Isolated Bilateral Renal Extramedullary Plasmacytomas.

Plasmacytomas are rare immunoproliferative monoclonal plasma cell diseases of lymphoid lineage that may present in an isolated or systemic manner. Systemic involvement is much more common than occurrences isolated to a particular organ, and for this reason, it is imperative to rule out systemic involvement for osseous and nonosseous isolated neoplasms. These neoplasms present unique challenges due to their location, extent of involvement, vague presentation, and dearth of treatment protocol. We report the case of a 69-year-old man who developed chronic kidney disease stage 4 between 2009 and 2012. Precipitous kidney failure, anorexia, fatigue, and flank pain necessitated clinical follow-up that ultimately led to thorough imaging and bilateral kidney biopsy. Protein electrophoresis, immunohistochemistry, and immunofluorescence were all consistent with bilateral renal extramedullary plasmacytomas. Treatment recommendations are often limited to prior case successes; however, chemotherapy, radiation, and surgery are the mainstay of treatment. Although surgery or combined therapy provides the best results for patients, such options are unfeasible with bilateral kidney involvement. Therefore, a chemotherapy regimen, similar to that for multiple myeloma, was determined to be most reasonable. Treatment consisted of 4 cycles of a bortezomib, cyclophosphamide, and dexamethasone regimen. Three months following chemotherapy, kidney function returned to baseline levels.

Secondary Skin Plasmacytomas.

A 78-year old man was diagnosed in 2006 with IgAκ multiple myeloma (MM) (stage III-A). The patient was referred to our dermatology department in 2012 for evaluation of erythematous skin nodules on the anterior right aspect of the thorax; the skin lesions were noted during hospitalization for multiple bone fractures. He was on fourth-line chemotherapy (with vincristine/adriamycin/dexamethasone) because of constant disease progression. The patient was unaware of the skin lesions' evolution over time and did not recall when they had first appeared. He had no pain, itching, or spontaneous bleeding.

Blastic plasmacytoid dendritic cell neoplasm with leukemic presentation: 10-Color flow cytometry diagnosis and HyperCVAD therapy.

Few studies describe the comprehensive immunophenotypic pattern of blastic plasmacytoid dendritic cell neoplasm (BPDCN) in the bone marrow and its treatment. This retrospective analysis evaluates the diagnostic flow cytometry (FCM) pattern and outcome of nine patients diagnosed with BPDCN. A four-tube 10-color FCM panel used for diagnosis of acute leukemia (AL), showed cells in the blast gate (CD45dim/low SSC) and were positive for CD4(bright), CD33(dim), CD56(heterogenous), CD123(bright), CD36, CD38, HLA-DR, CD71. Seven patients received front-line induction therapy with HyperCVAD with an overall response rate of 86%. Five of six responders underwent planned allogeneic hematopoietic cell transplantation (allo-HCT). For a median follow up of 13.3 months, the 1-year disease free survival and overall survival were 56 and 67%, respectively. An accurate diagnosis of BPDCN can be made by 10-color FCM using a four-tube AL panel demonstrating a characteristic pattern of antigen expression. Front-line induction chemotherapy with HyperCVAD can yield high remission rates, but allo-HCT is required for long-term durable remissions.

Primary pulmonary plasmacytoma: a case report introduction.

BACKGROUND: Extramedullary plasmacytoma is a rare plasma cell neoplasm within soft tissue and without bone marrow involvement or other systemic characteristics of multiple myeloma. Primary pulmonary plasmacytoma is a rare type of extramedullary plasmacytoma. CASE PRESENTATION: A 48-year-old male with a tumor in the right middle ear was referred to our hospital. A routine chest X-ray was arranged and showed enlargement of the left lung hilum. His bilateral breathing sounded clear. A chest CT scan revealed a well-circumscribed mass. Pathological biopsy yielded a diagnosis of isolated pulmonary plasmacytoma. CONCLUSIONS: This is the first presentation of primary pulmonary plasmacytoma with a solitary pulmonary nodule and no lymph node involvement.

Development of extramedullary myeloma in the era of novel agents: no evidence of increased risk with lenalidomide-bortezomib combinations.

Proteasome inhibitors (PI) and immunomodulatory agents (IMIDs) have improved the overall survival (OS) of patients with multiple myeloma (MM), but concerns have been raised about increased incidence of extramedullary disease (EMD) after the combined use of PIs and IMIDs for upfront therapy. We evaluated whether the addition of lenalidomide to bortezomib-based front-line regimens precipitated earlier development of EMD. We reviewed the charts of 117 MM patients (median follow-up from diagnosis 6·1 years; range 0·1-10·2 years) enrolled in eight clinical trials of first-line treatment with bortezomib-based regimens, with or without lenalidomide. We assessed development of EMD as extraosseous (distant from bone) or osseous (originating from bone) plasmacytomas. The primary endpoint was time from diagnosis until development of EMD, based on imaging, biopsy and/or physical examination. Any form of EMD at progression was observed in 40 (34·2%) patients, including 21 (18%) osseous, 8 (7%) extraosseous and 11 (9%) both osseous and extraosseous. Median OS was 0·9 years (range 0·1-4·8 years) after extraosseous EMD development. Sensitivity analyses with follow-up times truncated at 5 years detected no statistically significant difference in rates of any EMD form between the two groups (P > 0·2 for each comparison). Therefore, we observed no evidence that bortezomib-lenalidomide-based front-line therapy precipitates earlier EMD.

Isolated extraocular muscle infiltration with plasmacytoma treated with localized injection of dexamethasone.

Plasmacytoma of the orbit secondary to multiple myeloma is rare and has not previously been reported limited to an extraocular muscle. Conventional treatment is either localized radiotherapy or systemic chemotherapy. We report a case of plasmacytoma within the medial rectus muscle, which regressed completely with localized infiltration of dexamethasone.

[Bisphosphonate-associated osteonecrosis of the jaw]. / Bisphosphonat-assoziierte Kiefernekrosen.

BACKGROUND: Bisphosphonates (BP) are used in the treatment of severe osteoporosis and metastasis of malignant diseases. A possible relationship between the occurrence of osteonecrosis of the jaw and BP therapy was first described in 2003. Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is difficult to treat. In some cases the condition of the patients is so compromised that only minimally invasive surgery is possible. Histopathologically, osteonecrosis shows the features of chronic sequestered osteomyelitis, which can be found in different areas of the upper and lower jaw. Sometimes extensive resections of the jaw are necessary. Thus, BRONJ can cause mutilation, impairment of function and esthetics in the orofacial system and, thereby, compromise the life quality of the patients. Triggering factors are often tooth extraction without surgical plastic wound closure of the alveoli, but can also be associated with bruises from denture or other minor wounds. OBJECTIVES: The purpose of this article is to present results from our own patient collective, including therapy regime, success rate, and therapy recommendations. METHODS: The patient populations at three German hospitals were analyzed using a standard questionnaire. The patients in the study group, entered into a follow-up system for early detection of possible BRONJ, were evaluated for treatement outcome. RESULTS: The success rate for prophylactic surgery in asymptomatic patients was very high at 96 %. In the group with symptomatic BRONJ, the outcome was significantly lower (76.4 %). CONCLUSIONS: Because of the complex symptoms, close cooperation between oncologists, dentists, and maxillofacial surgeons is required in the treatment of BRONJ. Before starting therapy with bisphosphonates and during the therapy, dental treatment and monitoring of the patient' oral health is necessary.

The impact of intra-clonal heterogeneity on the treatment of multiple myeloma.

It is clear that cancers comprise a mixture of clones, a feature termed intra-clonal heterogeneity, that compete for spatial and nutritional resources in a fashion that leads to disease progression and therapy resistance. This process of competition resembles the schema proposed by Darwin to explain the origin of the species, and applying these evolutionary biology concepts to cancer has the potential to improve our treatment strategies. Multiple myeloma (MM) has a unique set of characteristics that makes it a perfect model in which to study the presence of intra-clonal heterogeneity and its impact on therapy. Novel therapies have improved the outcome of MM patients, increasing both progression-free and overall survival. Current therapy comprises an induction, consolidation and maintenance phases and it is important to consider how these components of MM therapy are affected by the presence of intra-clonal heterogeneity. In this evolutionary context therapy can be considered as a selective pressure differentially acting on the myeloma clones and impacting on their chances of survival. In this review current knowledge of intra-clonal heterogeneity, as well as its impact on the different components of MM treatment is discussed.