UNASSIGNED: Waldenström\'s macroglobulinemia (WM) is defined as a lymphoplasmacytic lymphoma (LPL) with immunoglobulin M (IgM) monoclonal gammopathy and morphologic evidence of bone marrow infiltration by LPL. Immunophenotyping and genotyping provide a firm pathological basis for diagnosis and are particularly valuable in differential diagnosis between WM and related diseases. Emerging technologies in mutational analysis present new opportunities, but challenges remain around standardization of methodologies and reporting of mutational data across centers.
UNASSIGNED: The review provides an overview of the diagnosis of WM, with a particular focus on the role of immunophenotyping and genotyping.
UNASSIGNED: Demonstration of LPL with a bone marrow biopsy is essential to reach a definitive diagnosis of WM. However, MYD88L265P and a typical WM immunophenotypic profile are valuable for the differential diagnosis of WM and related diseases, such as marginal zone lymphoma, multiple myeloma, and chronic lymphocytic leukemia. These methodologies must be utilized across centers and with appropriate standards followed in the evaluation and reporting of sensitivities and specificities. The diagnostic and/or prognostic value of mutations in genes such as CXCR4 and TP53 that are currently not routinely evaluated in the diagnosis of WM should be explored.

High-dose chemotherapy (HDCT) with autologous stem cell transplantation (ASCT) is an option to consolidate remission in Waldenstrom\'s macroglobulinemia (WM), particularly in selected younger patients with chemosensitive disease. BEAM, consisting of BCNU, etoposide, cytarabine, and melphalan, is often used as a conditioning regimen. However, problems with BCNU, including pneumotoxicity, tolerance, and availability, necessitate the search for alternatives. In this pilot study, we investigated high-dose chemotherapy with BeEAM, in which BCNU is replaced with high-dose bendamustine as an alternative conditioning regimen in six subsequent patients with WM. Bendamustine treatment was well tolerated without unexpected toxicities. The overall response rate was 6/6 patients (2 very good partial responses (VGPR) and 4 PR). After a median follow-up of 72 months, two (33%) patients relapsed. Median progression-free and overall survivals were not reached, and no severe late-onset toxicities were observed so far. In this pilot study, BeEAM conditioning before ASCT seems feasible, safe, and effective in patients with WM.

Macroglobulinemia is associated with Schnitzler syndrome (SchS) and Waldenstrom macroglobulinemia (WM). The aim of this article was to review the above-mentioned two diseases from clinical aspects and their potential genetic links. We performed a PubMed search using the following keywords: \"SchS,\" \"WM,\" \"autoinflammatory disease,\" \"periodic fever syndrome,\" and \"nucleotide-binding oligomerization domain containing protein 2 (NOD2).\" A case is exemplified. Both SchS and WM share some clinical phenotypes, and SchS can evolve into WM. Though no genetic link to SchS has been established, myeloid differentiation primary response gene 88 (MyD88) mutations are detected in one-third of SchS patients and 86% WM patients. Genetic analysis of periodic fever syndrome genes has detected NOD2 mutations in 18% SchS patients and rarely NLRP3 mutations. The literature data suggest that both MyD88 and NOD2 mutations may contribute to SchS. Both MyD88 and NOD2 are known to play important roles in innate immune response, and they may be cooperative in certain autoinflammatory diseases. Molecular analysis of NOD2 mutations may be incorporated into genetic testing for patients with suspected SchS or SchS/WM.

Treatment options for Waldenström\'s Macroglobulinemia (WM) have expanded rapidly in the last decades. However, there is no consensus on a preferred treatment. Therefore, patient preferences become increasingly important in making individualized treatment plans. Still, WM patients\' priorities and perspectives regarding their treatment options are unknown. We evaluated treatment preferences of WM patients using a discrete choice experiment (DCE).
A mixed-method approach was utilized for identification and selection of attributes/levels. The DCE questionnaire included five attributes: type of agent (targeted versus chemotherapy); frequency and route of administration; 5-year progression-free survival (PFS); adverse events; and risk of secondary malignancies. An orthogonal design and a mixed logit panel data model were used to construct choice tasks and assess patient preferences, respectively.
Three hundred thirty WM patients participated in the project. In total, 214 (65%) complete questionnaires were included for data analysis. The 5-year PFS, followed by risk of secondary malignancies were the most important attributes for making treatment choices. Regarding side effects, patients chose to avoid neuropathy the most compared to nausea/vomiting and extreme fatigue. Patients preferred a fixed-duration treatment with IV/SC administration at the hospital over a continuous daily oral regimen at home.
These are the first systematic data obtained on WM patient preferences for treatment. The results may help discussions with individual patients about their treatment choices. Also, these data can help design clinical trials in WM and inform health-care decision-making regarding outcomes that are most relevant to patients.

This report describes a case of disseminated nocardiosis, caused by Nocardia vulneris, in a 61-year-old man with macroglobulinemia and presenting with repeated fever, cough, shortness of breath, and muscle pain. The isolated Nocardia strain was resistant to ciprofloxacin, but susceptible to amikacin, gentamicin, tobramycin, linezolid, trimethoprim-sulfamethoxazole, amoxicillin/clavulanic, moxifloxacin, ceftriaxone, cefotaxim, and imipenem. The patient was started on combined meropenem and doxycycline treatment, followed by trimethoprim-sulfamethoxazole, which was subsequently switched to a combination treatment of linezolid, amikacin, and trimethoprim-sulfamethoxazole. The patient recovered, and his condition remained stable. Although infection by Nocardia vulneris is rare, and it is easy to miss detection in clinical practice, clinicians should be aware of the possibility of this infection. In addition, the MIC value of the drug sensitivity test should be ascertained when there is a wide choice of medicines. The current case was treated successfully with linezolid, amikacin, and trimethoprim-sulfamethoxazole. In cases of disseminated nocardiosis, the patient should be treated with antimicrobial therapy for at least 12 months. Furthermore, bacteriological examination and antimicrobial susceptibility testing should be performed regularly.

Ureteral amyloidosis is a rare entity and of interest to urologists, hematologists, radiologists, and pathologists because it mimics urothelial cell carcinoma clinically, endoscopically and radiologically. A pre-operative ureteroscopy or surgical biopsy is required, and it is essential to exclude systemic amyloidosis. We report a male who was diagnosed with IIIA stage lymphoplasmacytic lymphoma associating systemic amyloidosis with concomitant hematuria. Urine cytology was negative and computerized tomography urography (CTU) scan evidenced bilateral, proximal and medium, ureteral stenosis and wall thickening. Diagnosis of suspected amyloidosis was confirmed with laparoscopic biopsy due to ureteral stenosis, being positive for Congo red stain. Patient underwent systemic chemotherapy.

Diffuse and nodular glomerulosclerosis is associated with diabetic nephropathy and occasionally with tobacco users. However, it has also been linked with amyloidosis, cryoglobulinemia, and light-chain deposition disease. To the best of our knowledge, there is no published data on diffuse and nodular glomerulosclerosis without light chain deposition in Waldenstrom\'s macroglobulinemia (WM). We present a case of diffuse and nodular glomerulosclerosis in a non-diabetic, non-smoker with WM.

The article describes a clinical case of bilateral occlusion of retinal vessels in a patient with Waldenstrom\'s disease - a rare lymphoplasmocytic tumor of the bone marrow characterized by a complex of syndromes, among which the syndrome of blood hyperviscosity dominates. Comprehensive clinical, instrumental and laboratory examinations revealed that besides the syndrome of blood hyperviscosity the patient also had loci of cerebral ischemia (according to magnetic resonance imaging), ocular hypoperfusion with severe deficiency of retinal and choroidal blood flow (according to Doppler methods) indicating the presence of ocular ischemic syndrome. Since bilateral occlusion of retinal vessels without concomitant vascular and/or systemic pathology is rare, patients with such diagnosis should be referred to a hematologist.
В статье представлен клинический случай двусторонней окклюзии ретинальных сосудов при болезни Вальденстрема (БВ) - редкой лимфоплазмоцитарной опухоли костного мозга, характеризующейся совокупностью синдромов, среди которых доминирует синдром гипервязкости крови. В результате комплексного клинико-инструментального и лабораторного обследования у пациентки, помимо синдрома гипервязкости крови, выявлены очаги ишемического поражения головного мозга (по данным магнитно-резонансной томографии), гипоперфузия глаза с выраженным дефицитом ретинального и хориоидального кровотока (по результатам допплеровских исследований), что может свидетельствовать о наличии глазного ишемического синдрома. Поскольку двусторонняя окклюзия ретинальных сосудов без сопутствующей сосудистой и/или системной патологии встречается редко, пациентов с таким диагнозом следует направлять на консультацию к гематологу.

We report a case of Waldenström\'s macroglobulinemia (WM) treated using clarithromycin (CAM) and prednisolone (PSL). An 84-year-old woman was admitted to our hospital for bleeding after a tooth extraction and hematuria. Computed tomography showed multiple ill-defined nodules in the omentum (omental cake). Although the cause of the omental cake remained unclear, the patient was diagnosed with WM, based on the detection of M-protein of immunoglobulin (Ig) M in serum and lymphoplasmacytes in bone marrow. The bleeding tendency in the patient may have been due to acquired hemophilia and/or hyper IgM-induced platelet dysfunction. The patient was treated using CAM (800 mg/day) and PSL (10 mg/day). As a result, IgM levels gradually decreased. Because the omental cake contracted along with improvement in IgM, it was thought to be lymphoplasmacytic lymphoma-like lymphoma. This case shows that treatment using CAM and PSL may be effective in some cases of WM.

Waldenstrom macroglobulinemia (WM) is a lymphoplasmacytic lymphoma that presents with symptomatic anemia, thrombocytopenia, constitutional symptoms, extramedullary disease and rarely hyperviscosity syndrome. The presence of both IgM monoclonal protein and ≥10% monoclonal lymphoplasmacytic cells is required for the diagnosis. MyD88 is present in 67-90% of patients but is not pathognomonic for WM. Many patients who fulfill the criteria of WM are asymptomatic and do not require treatment. Recent advances in the understanding of the biology of WM have paved the way for new treatment options. The use of novel agents with or without rituximab enables the use of effective chemotherapy-free regiments upfront and in the relapsed setting. New targeted treatments such as venetoclax and CXCR4 antagonists are being investigated.