June 2026 Research Update

Taken together, these reports show that unicentric Castleman disease (a single enlarged lymph node area) often can be fully removed with surgery, and many patients remained stable afterward. At the same time, imaging often could not definitively distinguish unicentric Castleman disease from other tumors before surgery, especially when the mass was in uncommon locations. The strongest evidence in this group comes from one small retrospective series; the rest are single-patient case reports. [1] [2] [3] [4] [5] [6]

In a 24-person head and neck series, highly vascular masses were common on preoperative imaging, and most patients had complete remission in the operated area after resection. Two patients developed atypical postoperative issues (new nearby lymph node enlargement in one, ongoing fever in another) and, after cancer and infection were ruled out, both remained clinically stable with multidisciplinary follow-up. [1]

Several single-patient reports described unicentric Castleman disease appearing in uncommon places where it initially looked like a different condition, such as a lacrimal gland mass near the eye, an adrenal mass, a renal hilar (kidney blood vessel area) mass, and a lung nodule suspected to be cancer. In these reports, pathology after surgery confirmed the hyaline vascular type, and follow-up showed no recurrence at 12 months for the adrenal and renal hilar cases and at 24 months for the lung case. [2] [5] [3] [6]

One case involved the spine, where an epidural mass caused spinal cord compression symptoms; the mass was surgically removed and the patient regained the ability to walk independently. Follow-up imaging showed the epidural mass had been fully removed but some residual disease remained in the nearby vertebral bone, so the patient was given rituximab after surgery and involved-site radiotherapy was planned. [4]

Surgical complexity and risks varied by location, especially for very vascular tumors near major blood vessels. In the renal hilar case, preoperative imaging suggested a hypervascular retroperitoneal tumor and the patient ultimately had an open nephrectomy with substantial blood loss; the authors emphasized that diagnosis before surgery can be challenging and discussed the potential value of tissue diagnosis to help avoid unnecessary kidney removal in some situations. [3]

For patients and caregivers, this group of studies mainly reinforces a general pattern: when unicentric Castleman disease can be completely removed, follow-up in these reports was often reassuring, including in several rare body locations. However, these papers also show that before surgery the mass may look like other tumors on scans, and outcomes can depend on where the mass is located and how close it is to important structures (like major blood vessels or the spinal cord). Uncertainty remains because most evidence here comes from single-patient reports and one small single-center series, so results may not apply to everyone.

Across these papers, imaging was used to help clinicians sort out which Castleman disease subtype or related condition might be present, based on where changes show up in the body. One study suggested that lung findings may be less helpful in HHV-8 related multicentric Castleman disease, while lymph nodes and abdominal organ involvement may be more typical. A separate single-patient report showed how a whole-body scan can highlight widespread inflammation in the mouth and skin in a rare, serious immune skin condition linked to a tumor that arose from Castleman disease. [7] [8]

In a retrospective, single-center CT study comparing several HIV-associated conditions and multicentric Castleman disease types, no lung lesions were seen in HHV-8 related multicentric Castleman disease (hMCD), while other groups showed distinct lung patterns. The authors noted that if lung masses are present even when hMCD is confirmed, imaging could raise the possibility of a concurrent HIV-associated lymphoma. [7]

The same CT study also reported that lymph node enlargement and liver and spleen enlargement differed between the HIV-associated groups, and these abdominal findings were more common in hMCD than in idiopathic multicentric Castleman disease not otherwise specified (iMCD-NOS) without lung lesions. In iMCD-NOS, people who had lung lesions more often had disease seen in four or more body sites than those without lung lesions. [7]

A case report described one patient whose Castleman disease had transformed into a pelvic follicular dendritic cell sarcoma and was linked to paraneoplastic pemphigus, an immune blistering condition. On FDG PET/CT, the scan showed intense uptake in the mouth, patchy widespread uptake in the skin, a line of uptake in the upper esophagus, a focal spot in the anus, and mixed uptake in the pelvic tumor, suggesting that a scan pattern of widespread mouth and skin activity can fit with this type of paraneoplastic mucocutaneous disease. [8]

For patients and caregivers, these studies mainly add background on how scans may help doctors narrow down what type of Castleman disease or related condition is most likely, based on which organs are involved. The CT results come from one center and may not match every patient, and the PET/CT report describes only one person, so it cannot show how often that scan pattern occurs. What remains uncertain is how reliably these imaging patterns separate subtypes across different hospitals and patient groups, and how often overlapping conditions occur.

Across two retrospective studies, the main message was that interleukin-6 (IL-6) and C-reactive protein (CRP) do not behave the same way across treatments in idiopathic multicentric Castleman disease (iMCD), which matters for monitoring. CRP generally moved downward with effective IL-6 blocking therapy, while IL-6 itself could rise sharply during IL-6 blocking treatment, making IL-6 harder to interpret in that setting. In contrast, when patients were treated with therapies that do not directly block IL-6, IL-6 trends over time were more likely to reflect whether inflammation was improving or returning. [9] [10]

In a small study of 17 adults with iMCD, CRP decreased strongly after tocilizumab, while IL-6 increased dramatically, showing that blocking the IL-6 pathway can lead to higher measured IL-6 in the blood even as inflammation markers improve. In the same study, rituximab led to smaller decreases in both IL-6 and CRP that did not reach statistical significance. These different patterns suggest that the same lab test may mean different things depending on which drug is being used. [9]

In a larger single-center study of 149 people with iMCD, baseline IL-6 levels varied by subtype and were linked with other lab abnormalities, but baseline IL-6 did not predict who would have a biochemical response. Among people receiving non-IL-6 blocking regimens, IL-6 fell more in those who responded, and rising IL-6 could come before biochemical worsening. By contrast, during IL-6 blocking therapy, IL-6 often increased and did not track with biochemical response. [10]

For patients and caregivers, these studies help explain why an IL-6 result may look confusing during treatment that blocks IL-6, because the blood level can rise even when other inflammation measures improve. They also suggest that IL-6 trend monitoring may be more informative when a person is on treatments that do not directly block IL-6, while CRP may better reflect changes during IL-6 blocking therapy. Important uncertainties remain because both studies were retrospective, and results may differ by iMCD subtype and by the specific treatment plan used. [9] [10]

Three case reports described intensive, individualized treatment in idiopathic multicentric Castleman disease (iMCD), including severe TAFRO features and a refractory plasmacytic form. Overall, these reports show that some patients can have major improvements in inflammation and organ function, but each report reflects one person and cannot predict outcomes for others. They also highlight that treatment courses may involve switching therapies or managing treatment-related side effects. [11] [12] [13]

One report described a 31-year-old pregnant woman with iMCD with TAFRO features and acute kidney injury, where weekly siltuximab plus high-dose steroids was followed by rapid improvement in kidney and breathing function and stopping kidney replacement therapy after the second dose. A rash occurred before the third infusion, and the team switched from siltuximab to tocilizumab with rash resolution. The paper also discussed kidney biopsy patterns seen in iMCD-TAFRO (including thrombotic microangiopathy changes) and possible biological pathways involved. [11]

A second report described a 46-year-old woman with TAFRO syndrome who reached complete remission after a tocilizumab-based combination approach that also included other therapies, with imaging improvement in fluid buildup and lymph node changes. The remission lasted for more than three years without maintenance therapy, but the authors noted that multiple treatments were given together, so the specific contribution of tocilizumab cannot be isolated. This illustrates the challenge of interpreting outcomes when several treatments overlap. [12]

A third report described a 31-year-old woman with HHV-8-negative iMCD with idiopathic plasmacytic lymphadenopathy who received a single autologous CD19 CAR T-cell infusion after lymphodepletion and achieved a complete clinical and biochemical remission lasting more than 12 months. Side effects included mild cytokine release syndrome and low antibody levels that required intravenous immunoglobulin replacement. The authors proposed that, at least in this patient, targeting B cells may have been central to controlling disease activity. [13]

For patients, these case reports mainly serve as background evidence showing the range of treatment approaches used in rare, severe, or treatment-resistant forms of iMCD, including cases with kidney failure and complex systemic symptoms. They also show that side effects and supportive care (for example, kidney replacement therapy or immunoglobulin replacement) can be part of the overall treatment journey in selected situations. What remains uncertain is how often these outcomes occur in broader patient groups, because single-patient reports cannot separate the effects of one drug from the many other factors that may influence recovery. [11] [12] [13]

Across this months papers, Castleman disease was linked to complications outside lymph nodes, especially nerves, kidneys, and the eyes. The reports suggest inflammation-related signals (such as interleukin-6 and VEGF) may track with symptoms in some people, but evidence is limited because all reports describe single patients. [14] [15] [16] [17]

One patient with idiopathic multicentric Castleman disease developed repeated, sudden episodes of demyelinating polyneuropathy, a type of nerve problem that can cause major weakness and loss of walking ability. Testing showed nerve signal changes, spinal fluid changes, certain anti-nerve antibodies, and very high interleukin-6 levels, and a lymph node biopsy confirmed the Castleman disease diagnosis. [14]

Another patient with idiopathic multicentric Castleman disease not otherwise specified had progressive polyneuropathy along with Sjogrens syndrome and membranous nephropathy (a kidney condition that can cause protein to leak into the urine). After a multi-drug approach did not help and another therapy was not accessible, the report describes gradual neurologic recovery and protein in the urine resolving alongside near-normalization of interleukin-6 and VEGF while receiving rituximab alone over time. [15]

A separate kidney-focused case involved a teenager with nephrotic syndrome who was found to have Fabry disease coexisting with idiopathic multicentric Castleman disease and membranous nephropathy. The report describes protein in the urine and inflammation decreasing after steroid therapy, followed by stable Fabry-related blood markers and no return of proteinuria after enzyme replacement therapy. [16]

Eye involvement was described in a patient with POEMS syndrome associated with Castlemans disease, where both optic discs were swollen. Eye imaging showed thickening in the retinal nerve fiber layer and dye testing showed leakage, with visual field testing showing enlarged blind spots in both eyes and a defect in the left eye. [17]

For patients and caregivers, these papers mainly serve as background awareness that Castleman disease can sometimes be linked with nerve symptoms (numbness, weakness, walking difficulty), kidney leakage of protein, or eye/optic nerve swelling, and that other conditions can coexist and complicate the picture. Because each paper describes only one person, it is still uncertain how common these complications are, which blood markers reliably track them, and which approaches work best across different patients.

Across these small reports, the main message is that several different conditions can overlap with Castleman disease in symptoms and tissue appearance, which can lead to initial mislabeling. The papers highlighted confusion between immune system disorders, infections, skin-related plasma cell conditions, and lymphomas, especially when enlarged lymph nodes and abnormal blood proteins are present. Because these are case-based reports, they illustrate possibilities rather than giving firm estimates of how often this happens.

Two adults with prolonged fever and widespread enlarged lymph nodes were first thought to have lymph node diseases such as multicentric Castleman disease or a T-cell lymphoma based on biopsy, but were ultimately found to have a specific immune problem (anti-interferon-gamma autoantibodies) along with disseminated non-tuberculous mycobacterial infection. After antimycobacterial treatment (and rituximab in one patient), both had good clinical and scan-based improvement, showing how an underlying infection and immune problem can masquerade as a lymphoproliferative disorder. [18]

Two men with features of cutaneous plasmacytosis (a skin condition with many plasma cells) were discussed in relation to multicentric plasmacytic Castleman disease and IgG4-related disease, emphasizing that lymph node and skin biopsy patterns plus blood testing can point in different diagnostic directions. One patient had partial remission after anti-IL-6 therapy and combination immune-suppressing medicines, while the other remained stable for 12 months without treatment, suggesting the clinical course and treatment response can vary even within similar-appearing cases. [19]

A single case described a man with prior unicentric Castleman disease (hyaline vascular type) who later developed a new mediastinal lymph node that was diagnosed as nodular lymphocyte-predominant Hodgkin lymphoma on detailed pathology testing. He received R-CHOP chemotherapy, tolerated it well, and had no progression on follow-up imaging at the time reported, illustrating the diagnostic and care challenges when a new lymph node appears after unicentric Castleman disease. [20]

For patients and caregivers, these reports are most useful as background context for why the workup around enlarged lymph nodes, fevers, and certain skin findings can be complex, and why different conditions may be considered before a final label is reached. They also underline that infections and other immune-related diseases can resemble Castleman disease, and that new lymph node growth after unicentric Castleman disease may sometimes represent a different diagnosis. Because the evidence here comes from a few individual patients, it cannot show how common any of these scenarios are, or which people are most likely to experience them.

Across two case reports, doctors described how human herpesvirus 8 (HHV-8) can drive more than one condition at the same time, including Castleman disease and Kaposi sarcoma, and sometimes other related lymphomas. In these individual patients, remission was reported after targeted cancer therapies, but the reports cannot show how often these outcomes happen in others. [21] [22]

In one HIV-positive adult who was taking antiretroviral therapy, Kaposi sarcoma, multicentric Castleman disease, and extracavitary primary effusion lymphoma occurred together. After prior chemotherapy did not control the lymphoma, daratumumab alone was followed by complete metabolic remission on PET-CT and ongoing remission for more than two years, and the Kaposi sarcoma lesions also resolved. [21]

That same report tracked HHV-8 DNA in the blood and showed it fell during daratumumab treatment and later became undetectable. Tissue and single-cell analyses suggested CD38 (the protein daratumumab targets) was mainly seen in certain immune cells and plasma cells within these HHV-8 related diseases, rather than on Kaposi sarcoma tumor cells themselves. [21]

In a separate HIV-negative 58-year-old man, a lymph node biopsy confirmed HHV-8 associated multicentric Castleman disease along with Kaposi sarcoma, and the blood marker interleukin-6 (a signal linked to inflammation) was elevated. Treatment with rituximab plus pegylated liposomal doxorubicin was reported as well tolerated and was followed by clinical and lab-based remission. [22]

One laboratory study focused on how cells may naturally limit HHV-8 replication during its active (lytic) phase. It identified profilin 1 (PFN1) as a blocker of HHV-8 lytic replication by helping the cell use a selective recycling pathway (autophagy) to break down a viral protein needed for replication (ORF44). [23]

For patients and caregivers, these reports mainly add context about how HHV-8 can sometimes cause overlapping illnesses (Castleman disease, Kaposi sarcoma, and, more rarely, related lymphomas) and how clinicians may monitor both symptoms and blood markers while treating them. The remission outcomes came from single patients, so it is uncertain how well they apply to other people. The lab study is background research that helps explain possible ways the body can control HHV-8, but it does not yet tell what will work in people.