Though WM is commonly asymptomatic, clinical manifestations are well reported in the literature. The most common presentation is fatigue-related to normocytic anemia, in which the median Hb value is 10 g/dL [4], with other common symptoms including hepatomegaly (20%), splenomegaly (15%), and lymphadenopathy (15%). The reason behind these clinical presentations lies behind the circulation, tissue deposition, and autoimmune properties of IgM monoclonal proteins leading to hyperviscosity. Manifested hyperviscosity has been shown in roughly 15% of cases and with multiple neurological abnormalities, visual defects, and epistaxis [5]. WM patients have not reported before in literature with only headache or blurred as in our case.
Other less common presenting symptoms include cryoglobulinemia and cold agglutinin hemolytic anemia (5%), peripheral neuropathies (5–10%), and amyloidosis (2%). Extramedullary involvement sites have also been sighted through histological examination. Pei Lin et al. [6] stated that lymphoplasmacytic lymphoma was the most common histological type, in 40 (78%) samples from total 51 specimens obtained from lymph nodes (n=36), soft tissue (n=4), spleen (n=3), skin (n=2), lung (n=2), tonsils (n=1), colon (n=1), liver (n=1), and gallbladder (n=1). With only one pancreatic involvement in literature, WM affects the gastrointestinal tract, most commonly the stomach [7]. Furthermore, associated psychiatric complications to WM are still unclear, yet it can be attributed to Bing-Neel syndrome, in which the central nervous system is infiltrated by WM malignant clones complicating WM case with psychiatric symptoms as happened in our case [8].
Although clonal monoclonal gammopathy of undetermined significance MGUS B cells already contain the malignant molecular signature, all patients have an earlier phase of IgM (MGUS) that passed unnoticed. With median survival for patients under the age of 70 of 10 years or more, WM has lower median survival in older age groups, approximately 7 and 4 years for those 70–79 and those 80 or older, respectively [9] and with an incidence rate higher in males than females with 0.92 per 100,000 person-years to 0.30 [10].
WM diagnosis depends on both non-invasive and invasive procedures. Non-invasive measures mainly consist of serum and 24-h urine collection for protein electrophoresis, Serum immunofixation to confirm the IgM heavy and light chains, and quantitative test for immunoglobulin G immunoglobulin A and IgM. Invasive measures: Bone marrow biopsy which displays intertrabecular monoclonal lymphoplasmacytic infiltrate ranges from predominantly lymphocytic cells to overt plasma cells. As other associated symptoms should not be denied, computed tomography (CT) of the abdomen and pelvis must be done to detect organomegaly, lymphadenopathy, and serum viscosity is required when signs and symptoms of hyperviscosity syndrome are manifested or when IgM > 4000 mg/dL.
Low volume lymphoma or hematological malignancies medical center along with inaccuracy estimate of WM incidence and prevalence are the main reasons behind the many undiagnosed WM cases despite the vast amount of cancer registry data provided. Moreover, the reason lies behind the rarity of the disease, in addition to other significant limitations. The absence of the differentiation among IgM monoclonal gammopathy of asymptomatic WM and symptomatic WM requiring therapy treatment is the most critical limitation [11]. Diagnostic criteria and method modifications that occurred over the past 30 years are also part of the limitations and inaccuracy of the retrospective registries [11]. With the continuous change in the diagnostic criteria, the treatment guidelines are in constant evolution. Yet, the main lines of treatment contain two main core treatments: treating the associated symptoms, especially hyperviscosity syndrome, and reducing tumor mass.
Although affecting a decreasing portion of patients nowadays, hyperviscosity syndrome is rarely symptomatic, it makes treatment challenging. Symptoms such as epistaxis, gingival bleeding, visual changes due to retinal hemorrhage, and central nervous system findings, including dizziness, light-headedness, and generalized fatigue, must be suspicious, and serum viscosity must be measured [12]. When hyperviscosity exists, plasma exchange should be carried out as a mainstay measure until systemic therapy successfully reduces the tumor mass and decreases the IgM protein serum concentration [12]. Variety of systemic chemotherapy to reduce tumor mass has been proposed in the literature and with supporting evidence. Lacking long-term toxicity and impact on the peripheral blood stem cells’ mobilization, Rituximab has shown the most significant impact in the treatment of WM. Drug utility is further increased when combined with ofatumumab, another monoclonal antibody [13].
Furthermore, many clinical trials have proposed the combinations between different interventions and even suggested using corticosteroids from their role in managing the inflammatory response. As for now, 4 different preferred standards of therapy are available for WM: (1) bendamustine and rituximab, (2) bortezomib and dexamethasone and rituximab, (3) ibrutinib ± rituximab, and (4) rituximab and cyclophosphamide and dexamethasone. Additional clinical studies comparing the response rates, tolerability, and the cost of these regimens are needed to aid physicians in tailoring the therapy to their patients according to the provided treatments such as carfilzomib, cladribine, and fludarabine are required to assist physicians in tailoring the treatment to their patients [14, 15].