A patient with a history of DLBCL presenting with a relapse confined to the skin without lymphadenopathy should raise suspicion. This presentation "smells a lot like Marginal Zone Lymphoma," a less aggressive cancer that may be managed differently, highlighting the need to question histology in atypical relapses.

Chronic low-grade inflammation often presents not as obvious swelling but as subtle, persistent symptoms. Issues like increased fatigue, difficulty concentrating, poor sleep, and skin problems can be driven by an under-the-radar inflammatory state that even doctors may miss.

There's a growing recognition that the molecular profile of a primary tumor can differ significantly from its metastases. To guide treatment more accurately, the preferred practice is to biopsy an accessible metastatic lesion when possible, as this better reflects the biology of the active disease being treated.

Plasmacytoid bladder cancer spreads locally along the urothelium, which can be missed on imaging. Clinicians must push for a thorough examination under anesthesia (EUA) before surgery, even if a patient shows a complete radiographic response to therapy.

A diagnosis of myelofibrosis without a JAK2, CALR, or MPL mutation should be treated as a red flag, not a final diagnosis. It warrants a deeper investigation for alternative causes, such as MDS/MPN overlap syndromes or secondary fibrosis from other conditions like autoimmune disease or hairy cell leukemia.

With new CNS-active drugs dramatically improving survival after a brain metastasis diagnosis, some experts are now advocating for routine screening brain MRIs in high-risk patients. The goal is to detect asymptomatic lesions early, potentially preventing catastrophic neurologic events like seizures.

When treating extramedullary disease (EMD), intravenous (IV) bortezomib should be used over the more common subcutaneous formulation. The higher peak drug concentration (Cmax) achieved with IV administration is critical for efficacy against these difficult-to-penetrate sanctuary sites.

When imaging is ambiguous between radiation necrosis and tumor progression in the brain, a short course of high-dose dexamethasone can serve as a diagnostic tool. Imaging improvement after steroids strongly suggests radionecrosis, potentially avoiding an invasive biopsy.

Mezigdomide is considered one of the most active oral agents against extramedullary disease (EMD). Its molecular structure was specifically engineered to optimize tissue penetration, addressing a significant clinical challenge where myeloma grows outside the bone marrow in heavily pretreated patients.