Extramedullary plasmacytoma of the tongue: A case report

Background: Tongue extramedullary plasmacytoma is a very rare pathology. Despite rare cases, extramedullary plasmacytoma should be considered as a differential diagnosis in case of a mass in the tongue. A total of 19 cases were reported with EMP in English literature along with the case we will address. It is characterized by a monoclonal neoplastic proliferation of plasma cells in the absence of multiple myeloma (MM). Histopathology and immunohistochemistry are very important for the diagnosis and differential diagnosis. Case presentation: The case we will describe is an 80-year-old lady from Albania who presents with a vegetative lesion in the form of a thick plate on the dorsal part of the tongue with dimensions 6 X 5 X 1.5 cm. A material of 0.5 cm diameter was taken from the lesion for the biopsy. After histopathological examination, immunohistochemical examinations, and after correlations with laboratory, clinical and imaging data, the diagnosis of extramedullary plasmacytoma of the tongue was reached. The patient underwent radiotherapy treatment. Conclusions: EMP is a rare tumor, accounting for 3% of plasma cell neoplasms and <1% of all head and neck tumors. The diagnosis of EMP, in this case, was reached with biopsy, immunohistochemistry, and the correlation with laboratory and imaging data. We will show the importance of biopsy along with immunohistochemistry in the diagnosis and differential diagnosis of extramedullary plasmocytoma of the tongue. Keywords: plasmacytoma; immunohistochemistry; biopsy; plasma cell. Abbreviations: EMP: Extramedullary plasmacytoma; MM: Multiple myeloma; Cm: centimeter

Solitary Ovarian Plasmocytoma: A Rare localization of Extramedullary Plasmocytoma. A Case Report

Background: Solitary plasmacytoma is a rare malignant neoplasm of plasma cells accounting 5-10% of all plasma cell dyscrasias with extramedullary plasmocytoma in 3- 5%. Their localization in the female genital tract is quite rare, either as solitary plasmacytomas or as part of a disseminated MM. Solitary ovarian plasmocytoma is extremely rare. Case: A 52-year-old woman, presented presented postmenopausal recurring episodes of metrorrhagia with left ovarian mass. She was diagnosed with solitary ovarianplasmocytoma without systemicdisease. The patient underwent complete surgery resection and a full work up to rule out multiple myeloma that objectived a small serum monoclonal protein that had resolved postoperatively. At 17 months of follow-up, the patient is still alive and doing well with no signs of recurrence or progression to mutliple myeloma. Although rare, solitary plasmacytoma of the ovary can occur without any overt symptoms or laboratory abnormalities tests and require prompt and adequate treatment and rigorous monitoring due to their ability to relapse or progress to MM. Complete surgical resection followed by activesurveillance is appropriate.

Clinical and Biological Characteristics of Medullary and Extramedullary Plasma Cell Dyscrasias

Background: Extramedullary plasma cell (PC) disorders may occur as extramedullary disease in multiple myeloma (MM-EMD) or as primary extramedullary plasmocytoma (pEMP)/solitary osseous plasmocytoma (SOP). In this study, we aimed to obtain insights into the molecular mechanisms of extramedullary spread of clonal PC. Methods: Clinical and biological characteristics of 87 patients with MM-EMD (n = 49), pEMP/SOP (n = 20) and classical MM (n = 18) were analyzed by using immunohistochemistry (CXCR4, CD31, CD44 and CD81 staining) and cytoplasmic immunoglobulin staining combined with fluorescence in situ hybridization (cIg-FISH). Results: High expression of CD44, a cell-surface glycoprotein involved in cell-cell interactions, was significantly enriched in MM-EMD (90%) vs. pEMP/SOP (27%) or classical MM (33%) (p < 0.001). In addition, 1q21 amplification by clonal PC occurred at a similar frequency of MM-EMD (33%), pEMP/SOP (57%) and classical MM (44%). Conversely, del(17p13), t(4;14) and t(14;16) were completely absent in pEMP/SOP. Besides this, 1q21 amplification was identified in 64% of not paraskeletal samples from MM-EMD or pEMP compared to 9% of SOP or paraskeletal MM-EMD/pEMP and 44% of classical MM samples, respectively (p = 0.02). Conclusion: Expression of molecules involved in homing and cytogenetic aberrations differ between MM with or without EMD and pEMP/SOP.

Solitary (extramedullary) plasmocytoma. Clinical recommendations

Solitary (extramedullary) plasmocytoma. Clinical recommendations

Rare Differential Diagnosis of Dyspnea: Extramedullary Plasmocytoma (EMP) of the Larynx—Case Report and Review of the Latest Literature of Laryngeal EMP and Laryngeal Involvement of Multiple Myeloma

Multiple myeloma (MM) of the larynx is extremely rare. It can be either a laryngeal manifestation of a general multiple myeloma or it can occur as a primary laryngeal mass, which is then called extramedullary plasmocytoma (EMP). We present the case of an 81-year-old male patient who was admitted for dyspnea. He had a history of multiple myeloma but was in complete remission since some years. Histological and immunohistological examination of tissue samples revealed an EMP. The patient was first treated by laser surgery in order to reduce the tumor mass and secure the airway. Afterwards, he was systematically treated by radiation therapy with 60 Gy, which achieved a good response and complete remission proven by control laryngoscopy and histological examination of tissue samples taken from the former tumor area three months after laser excision. The latest literature in the field is reviewed. There were only ten cases of EMP in the larynx or laryngeal involvement of MM published within the last five years (Pubmed was searched for “larynx,” “laryngeal” and “EMP,” “Extramedullary Myeloma,” “Multiple Myeloma,” and “MM”). Due to its rarity, there are currently no evidence-based therapeutic guidelines available. For their development, multicenter studies are required.

Treatment of Relapsed and Refractory Multiple Myeloma with Fully Oral Triplet IRD (ixazomib, lenalidomide and dexamethasone) Is Safe and with Significant Therapeutic Outcomes

Aims: Treatment of multiple myeloma (MM) in relapsed and refractory setting (RRMM) has been a challenge. The best outcomes have been observed in triplet combination of novel drugs. However, most combinations require weekly parenteral administration thus degrading patients´adherence to therapy, especially when treatment is scheduled "until progression". The introduction of fully oral triplet combination ixazomib, lenalidomide and dexamethasone (IRD) showed an outstanding efficacy in the Tourmaline-MM1 trial. Our aim is to determine the efficacy and safety of IRD regimen outside clinical trials. Patients and methods: A cohort of 127 RRMM patients from the Czech and Slovak Republic were treated with IRD regimen within a Named Patient Program between 2016 and 2018. The M/F ratio was 1.2:1 with median age 66 years (41-84). The representation of M-protein and light chain types as well as ISS stage was standard. The data for cytogenetics were recorded only at the time of diagnosis in 71% of patients with 15 patients having high-risk features - t(4;14), t(14;16) and del17, and 41 patients having standard risk features. In 34 patients we were not able to determine the risk status as at least one abnormality was missing and none was positive. The presence of extramedullary plasmocytoma was recorded in 15% of patients. Most patients received IRD for their 1st relapse (58.5%), followed by 2nd (23.7%) and 3rd relapse (7.6%) with significant portion of patients being treated in ≥4th relapse (10.1%). The pretreatment with individual drugs was as follows: bortezomib (BTZ) 94.5%, thalidomide (THAL) 40.9%, lenalidomide (LEN) 18.9% and carfilzomib 5.5%. 62.2% of patients underwent previous autologous stem cell transplant. Altogether 25.2% of patients were refractory to at least 1 drug with 18.9% being BTZ refractory and 7.9% LEN refractory. Data were analyzed from the Czech Registry of Monoclonal Gammopathies. Data were described by absolute and relative frequencies of categorical variables and mean (standard deviation), median (minimum-maximum) of quantitative variables. Survival measures were plotted using Kaplan-Meier methodology at 95% confidence interval, log-rank test was used to estimate the statistical significance at P<0.05. Results: The overall response rate to IRD regimen (≥ partial response, PR) was 67.1% with clinical benefit rate (≥ minimal response, MR) of 77.2%. The rate of individual responses was as follows: complete response (CR) in 11.4%, very good partial response (VGPR) in 16.5%, PR in 39.2%, MR in 10.1%, stable disease (SD) in 13.9% and progressive disease (PG) in 8.9%. The median overall survival was not reached after median follow up of 9.4 months. Median progression free survival (PFS) was 23.1 months. PFS was significantly decreasing with number of previous lines (not reached after 1 previous lines, 23.1 after 2 lines, 8.7 after 3 lines and 4.6 after ≥4 lines, p = 0,006). As expected, the best PFS increased with deeper therapeutic response (SD+PD = 4.1 months, MR = 9.0 months, PR = 15.1 months, VGPR = 13.2 months, and CR = median PFS not reached). There were limited information regarding the high risk features. Still, we confirmed adverse impact of the presence of extramedullary disease (PFS 5.5 vs 23.1 months, p = 0.001). Similarly, patients did worse when being pretreated by both proteasome inibitor and an IMiD versus solely proteasome inhibitor (PFS 10.0 vs 23.1 months, p = 0.001). The outcomes of high-risk cytogenetics were beyond statistical significance. Most toxicities were grade ≤2. Only hematological toxicity and infection reached grade 3 or higher, as follows: neutropenia in 35.1%, thrombocytopenia in 22.8%, anemia in 12.3% and infection in 19.3%. Conclusions: IRD regimen is very effective in RRMM. We confirmed its efficacy even in highly pretreated population (≥4 prior regimens) and in patients refractory to BTZ or LEN, which were exclusion criteria for the Tourmaline trial. The fully oral combination is well tolerated, with manageable side effects and easy management of dose modifications. Unlike the original trial our data show better results in patients with less pretreatment. The presence of extramedullary plasmocytoma deteriorates the prognosis of patients on IRD regimen. We thank to Takeda for enabling the Named Patient Program. With support of AZV 17-29343A, MH CZ - DRO (FNOl, 00098892) Disclosures Maisnar: Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees. Hajek:Amgen: Consultancy, Honoraria, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Research Funding.