Unicentric Castleman's Disease

Corey Casper, MD, MPH:Unicentric Castleman’s disease is a unique disease. Some would say it’s actually the most common variant of Castleman’s disease. Again, we don’t have great data on this, but some would say that up to 70% of Castleman’s cases are of the unicentric variant. The unicentric variant can come in two sub-variants: hyaline vascular variant or plasma cell variant. Unicentric hyaline vascular variant disease tends to be associated with very minimal symptoms.

Generally, the symptoms that present in these patients are attributable to an enlarged lymph node. So, the lymph node has grown so large that it can press on something else. I’ve seen many cases where a lymph node can be the size of a grapefruit, and obviously if they’re in the thorax, the abdomen, or the axilla, or even in the cervical chain, they can cause a number of local symptoms from the compression of that enlarged lymph node on the surrounding vascular or neurologic structures. For unicentric disease, I would say the most common presentation is an enlarged lymph node and that either will come to attention because clinically it’s causing other symptoms or because it’s picked up incidentally. For instance, I’ve had patients who were diagnosed with Castleman’s disease after being in a car accident and having a routine chest X-ray done at that time to look for rib fracture that shows an enlarged lymph node in the chest. I’ve had patients that have gone for executive physicals and have had chest X-rays as part of that, and, again, enlarged lymph nodes were detected that never caused any symptoms. So, for unicentric disease, the hallmark is an enlarged lymph node either with local symptoms because of compression or picked up incidentally because of other radiographic or medical testing.

Patients who have the unicentric plasma cell variant can have other constitutional symptoms that are associated with the disease. Most commonly, it is debilitating fatigue, night sweats, and fevers. Those are usually the constellation of symptoms, things that we typically call B symptoms that are associated with the plasma cell variant of unicentric disease. Finally, there is some controversy among experts in the field as to whether unicentric disease may sometimes represent an early presentation of multicentric disease. [The question is whether] unicentric disease may eventually evolve into the multicentric type or whether it’s its own distinct entity. I would say that for myself, I consider it its own distinct entity because I have a number of patients who have been observed for 20 or 30 years and never progressed beyond their unicentric manifestations. But even just yesterday in clinic, I saw a patient who 20 years ago was thought to have unicentric disease but then came back presenting with multiple enlarged lymph nodes 20 years later. It highlights how much we don’t know about Castleman’s disease. But I would say that, in general, unicentric disease is a distinct entity, typically with minimal symptoms, and that differentiates it from the multicentric variant.

As for unicentric disease, there’s a controversy as to whether or not to treat it and how aggressively to treat it. Generally, what would push you toward wanting to treat unicentric disease is when it has associated local symptoms. As you can imagine, it just depends on the location. I’ve seen unicentric disease in the cervical lymph node chain present with an inability to breathe, stridor, and difficulty because of compression on the trachea. On the other hand, disease in the axilla is generally uncomfortable, and patients present with pain and local symptoms related to just having a large lymph node in a small space. In the thorax, you can have a number of different compression syndromes. I’ve seen superior vena cava syndrome associated with a very large lymph node. Again, compression of nerves can lead to neurologic deficits. In the thorax and in the mediastinum where the disease was first described—again, because space is so limited–there could be a number of symptoms, usually vascular or neurologic related to compression.

In the abdomen, there’s generally more room for a lymph node to swell, but I have seen cases of bowel obstruction or other local symptoms of abdominal pain in the setting of enlarged lymph nodes with unicentric disease. So, if a patient were to have symptoms and the lymph node were deemed by the provider to be causing problems, the most common way that unicentric disease is dealt with is surgical resection. Generally, because the disease often requires a histologic biopsy, patients who present with a solitary enlarged lymph node will have a surgical excision of the entire node. And, in my experience, recurrences are very unusual. Usually surgical excision is definitive. There are cases where because of the location of the lymph node, surgical excision is not an option. In those cases, external radiation therapy can be an option; in other cases, chemotherapy or targeted biologic therapy. But the first-line therapy for unicentric disease generally is surgical excision.

The majority of patients with unicentric Castleman’s disease who undergo a surgical excision of a solitary lymph node will have no further recurrences, no additional symptoms, and outcomes are extraordinarily good. I will say that there have been cases, in my experience, of unicentric plasma cell disease where the resection of the lymph node itself does not lead to a reduction in some of the associated constitutional symptoms. Patients may have the mass removed, but may continue to have constitutional symptoms, like fevers or fatigue, or night sweats. Perhaps this is because there are microsatellite loci of the tumor or of the lymph node that are left behind, but I also would say that that’s a rarity. Even most patients with plasma cell variant unicentric disease, the overwhelming majority of more than 90% in my experience, will have no further symptoms for decades after surgical excision.

Corey Casper, MD, provides information on the diagnosis and treatment of patients with Castleman Disease (CD).