This post highlights in-depth breakdowns of my favorite clinical cases from May 2026. I then provide some commentary and build on the lessons from my own experience, where appropriate.
I’ve broken these cases into multiple parts to keep the length of each post more digestable.
Case Summary
A 64F with h/o BRCA2 presented with a subacute three-week course of progressive fatigue with cognitive changes, unsteady gait, and repeated falls. An MRI of the brain revealed numerous mildly expansile gadolinium-enhancing white matter lesions. These lesions featured both closed ring and open ring enhancement. An LP subsequently showed lymphocytic pleocytosis. Given uncertain diagnosis, a brain biopsy was performed to rule out malignancy or infection. Pathology showed a macrophage-rich inflammatory process with demyelinization and axonal preservation. Together, these were classic for demyelinating disease. A final diagnosis of Tumefactive Late-Onset Multiple Sclerosis was made. She was treated with high-dose corticosteroids and clinically improved. She was then started on long-term disease-modifying therapy.
Tumefactive Multiple Sclerosis (MS)
Tumefactive MS is a rare variant characterized by large tumor-like demyelinating lesions greater than 2 cm. It can be the initial manifestation of MS. Given it often presents with focal deficits, encephalopathy, and mass effect, the ddx initially is often quite broad and includes primary tumors like gliomas, lymphoma, and abscesses.
MRI is the most crucial non-invasive tool for diagnosis. You’ll see T2/FLAIR hyperintense lesions with an incomplete or “open ring” pattern of enhancement. In comparison, abscesses will show complete uniform rings, and high-grade gliomas will show thick irregular rings. These lesions will also lack central restricted diffusion that is characteristic of a pyogenic abscess.
CSF will often show a mild lymphocytic pleocytosis and elevated protein. The presence of CSF-restricted oligoclonal bans or an elevated free-capital light chain index is supportive of an MS diagnosis.
When biopsies are performed, histology will show an inflammatory infiltrate dominated by foamy :myelin-laden: macrophages. There will be a profound loss of myelin, but relative preservation of axons.
Management consists of high-dose IV corticosteroids for an acute attack, with plasma exchange as a second-line option. Patients have then started on long-term Disease Modifying Therapy (DMT) prevent future relapses and disability.
Pearls
Tumefactive MS is a great mimicker of CNS malignancy and infection
The ddx for ring-enhancing brain lesions is broad, and this diagnosis should always be considered.
The “open-ring” sign on contrast-enhanced MRI is a specific clue for demyelinating disease.
The absence of restricted diffusion within a ring-enhancing lesion is a critical imaging feature that makes a pyogenic abscess much less likely.
While MS is typically a disease of young adults, late-onset MS (after age 50) can occur and may present with an aggressive, tumefactive subtype.
My Commentary
In my opinion, a new brain lesion presents one of the more interesting differentials in all of medicine. Given my own clinical blind spots (I only care for MS patients these days if they happen to have it as a co-morbidity), I wasn’t even aware of tumefactive MS and the intricacies of how they appear on imaging. For me, it was a good reminder that not every space-occupying lesion that shows up in the brain is either malignant or infectious.
Case Summary
A 60M with housing insecurity presented with one week of painful blistering rashes and in one month history of nondescript constitutional symptoms. However, he was notably afebrile. Lab showed that he had a severe AKI along with anemia and thrombocytopenia. He progressed to renal failure and required hemodialysis. A skin biopsy showed leukocytoclastic vasculitis. A renal biopsy revealed a pauci-immune crescentic glomerulonephritis. Workup was otherwise notable for negative BCx, yet a TEE confirmed a mitral valve vegetation. The diagnosis of Bartonella quintana endocarditis was sealed when IgM and IgG serologies were positive. He was treated with a prolonged course of doxycycline and rifampin.
Bartonella quintana Endocarditis
Bartonella endocarditis is a classic cause of culture-negative endocarditis. Bartonella is a slow glowing GNR transmitted by the human body louse. It is historically associated with “trench fever”. It more commonly affects individuals experiencing homelessness, alcoholism, or crowded living conditions.
Clinical presentation is often sub-acute and may lack overt fevers. Patients also frequently present with complications of a chronic infection, such as heart failure from valvular destruction.
The diagnosis relies heavily on serology, given BCx are almost always negative. A high IgG antibody titer (specifically > 1:800), along with a positive IgM is consistent with the disease.
TTE/TEE typically reveal large friable vegetations. These are most commonly on the aortic or mitral valves.
Labs may show anemia, thrombocytopenia, and elevated inflammatory markers (ESR/CRP). Patients with glomerulonephritis will have hematuria, proteinuria, and elevated creatinine, and often low complement levels.
Treatment requires a prolonged course of abx. Typical regimens for native valve endocarditis include doxycycline for at least six weeks. This is often combined with an aminoglycoside such as gentamicin for the initial two weeks. Given its common to see extensive valvular damage and heart failure, valve replacement surgery is often needed.
Pearls
Bartonella is a leading cause of culture-negative endocarditis.
Given the presentation of Bartonella endocarditis can be insidious in a febrile, you should be alert for the evidence of immune-mediated complications such as glomerulonephritis or a vasculitic rash.
Do not rule out endocarditis based on negative BCx alone, especially when the clinical picture is suggestive. Diagnosis of Bartonella endocarditis relies on serology.
A low C3 with a normal C4 is a clue for an underlying infection-related glomerulonephritis.
My Commentary
This is such a great case given not only because of the the final diagnosis of culture negative endocarditis, but also because of the reminder that endocarditis is a systemic disease process and can lead to various immunological and other manifestations in various organs throughout the body, notably the kidneys in this case. It’s not easy to think about endocarditis and get an echo when BCx are negative, and it takes even more clinical gumption to be concerned enough to get a TEE when a TTE seems normal. In my experience caring for patients with Cx negative endocarditis, I was lucky enough to have the diagnosis sealed with TTE alone.
Case Summary
A 54M with pulmonary sarcoidosis presented with palpitations. He was treated with metoprolol. However, an implantable loop recorder captured polymorphic ventricular tachycardia (PMVT). Given his history of sarcoid, the team initially pursued a diagnosis of cardiac sarcoidosis. However, the patient had a negative cardiac MRI and PET scan. The patient then went on to develop paroxysmal severe HTN with diaphoresis and tremors. This new information prompted his PCP to test for pheochromocytoma. The patient had elevated urine metanephrines and a 3 cm adrenal mass on CT. Surgical resection resolved in a complete resolution of all of his arrhythmias and HTN.
Pheochromocytoma
Pheochromocytomas are rare neuroendocrine tumors of the adrenal medulla. They secrete catecholamines such as epinephrine and norepinephrine. The textbook presentation of pheochromocytoma is a triad of episodic headaches, diaphoresis, and tachycardia. However, the presentation can be highly variable. Most patients experience either sustained or intermittent HTN which can be difficult to control. Catecholamine excess can lead to cardiac manifestations including sinus tachycardia, SVT, ventricular arrhythmias, and stress-induced (Takotsubo) cardiomyopathy.
The initial screen is with plasma-free metanephrines or 24-hour urinary fractionated metanephrines. Both of these tests have high sensitivity.
Once these screens are positive, localization is performed with CT or MRI of the abdomen and pelvis. Functional imaging (MBG, DOTATATE) can be used if localization is difficult.
Management is largely focused on surgical resection. Prior to surgery, patients require preparation with alpha-adrenergic blockade with either phenoxybenzamine or doxazosin. This helps to control blood pressure and prevent intraoperative hypertensive crisis. Beta blockers are only added after adequate alpha blockade to help manage any reflex tachycardia.
Complete surgical removal of the tumor is often curative.
Pearls
Pheochromocytoma is another “great mimicker”. Catecholamine excess can lead to a number of bizarre symptoms including diverse arrhythmias and paroxysmal HTN.
Though they are not the most common manifestations, life-threatening ventricular arrhythmias like PMVT are possible
Initiating beta-blockers before alpha-blocker in a patient with a pheochromocytoma can lead to a hypertensive crisis
My Commentary
This case is a strong reminder of when anchoring on a seemingly straightforward manifestation of an already diagnoses disease can lead clinicians astray. I largely care for oncology patients in the hospital, and the bias of ascribing any symptom/presentation to chemo and/or their primary malignancy is one I fight against every single day. It can be challenging, however, when 99 times out of 100 this assumption is correct. This is why pattern recognition, and trusting your clinical intuition when something seems off, is so important.
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