iMCD: A mysterious condition that mimics many other diseases
About iMCD
Lymphadenopathy with an inconclusive diagnosis? Consider iMCD.
If you suspect that your patient might have lymphoma or myeloma but are unable to find a conclusive diagnosis, you may want to consider idiopathic multicentric Castleman disease (iMCD).
Understanding Castleman disease and its subtypes
Castleman disease (CD) describes a group of distinct, nonmalignant lymphoproliferative disorders with a shared histopathology.1,2
They are further classified as the following:
Multicentric Castleman Disease (MCD)
MCD involves multiple groups of enlarged lymph nodes and may require ongoing treatment to keep the symptoms under control.1,2
Unicentric Castleman Disease (UCD)
UCD involves a single group of enlarged lymph nodes and can be treated by surgically removing the affected lymph node.1,2
Subtypes of MCD
There are 3 known subtypes of MCD. Their classifications are based on the number of regions of enlarged lymph nodes and the presence or absence of human herpesvirus-8 (HHV-8) or the POEMS syndrome criteria.1-5
iMCD
A patient diagnosed with human immunodeficiency virus (HIV)–negative and HHV-8–negative MCD is classified as an iMCD patient.2
POEMS-associated MCD
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS)–associated MCD is defined by the presence of either bone lesions or a λ-restricted plasma cell disorder.3
HHV-8–positive MCD
This subtype of iMCD can cause Kaposi’s sarcoma—a rare cancer in which lesions grow on the skin, mouth, nose, throat, and other parts of the body.1,3-5
iMCD is a rare disease that can be difficult to diagnose, as its characteristics are similar to cancers such as non-Hodgkin lymphoma, autoimmune disorders such as rheumatoid arthritis, and infectious disorders such as HIV.3
Corey Casper, MD, MPHThe diagnosis of iMCD could be extremely challenging, and one initially has to rule out some of these other mimicking conditions.
Common symptoms of iMCD
The presentation of iMCD can vary from patient to patient. It can range from mild constitutional symptoms such as fever and night sweats to a life-threatening cytokine storm, which can lead to organ failure.3,6,7
Here are some of the most commonly observed symptoms:
Generalized Lymphadenopathy
Generalized Lymphadenopathy
Enlargement seen across multiple groups of lymph nodes2,3,7
Organomegaly
Organomegaly
Enlarged liver or spleen3,7
Night Sweats
Night Sweats
Repeated episodes of excessive sweating during sleep3,7,8
Flu-like Symptoms
Flu-like Symptoms
Fever, night sweats, cough, fatigue, and unintentional weight loss3,7,9
Fluid Accumulation
Fluid Accumulation
Edema, ascites, and/or other symptoms of fluid overload3,7
Subtypes of iMCD based on clinical features
Some patients with iMCD present with an intense inflammatory clinical subtype known as iMCD-TAFRO. The recently proposed definition for iMCD-TAFRO requires at least 4 clinical criteria (thrombocytopenia, anasarca, fever/hyperinflammatory status, and organomegaly [TAFO]), renal dysfunction or pathological feature in bone marrow such as reticulin fibrosis (R), and lymph node features consistent with iMCD.10
The majority of patients with iMCD, however, present with a subtype that is not otherwise specified (NOS) and is characterized by a less intense inflammatory syndrome, normal to elevated platelet counts, and polyclonal hypergammaglobulinemia.2,7
IL-6: An important signaling molecule that may become dysregulated
In some patients with iMCD, the levels of interleukin-6 (IL-6) may increase during flare-ups.2,7,11 Dysregulated IL-6 can be a key mediator of a cytokine storm, which can increase the following2,11,12:
- Growth of B cells
- Vascular endothelial growth factor (VEGF) signaling and angiogenesis
- Production of helper T cells (TH)
- Synthesis of acute phase proteins that can lead to various systemic symptoms of iMCD
An IL-6–driven cytokine storm may lead to systemic inflammation, multicentric lymphadenopathy, cytopenia, and potentially fatal multiple organ dysfunction.2
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About Castleman disease: what is Castleman disease? American Cancer Society. https://www.cancer.org/content/dam/CRC/PDF/Public/8594.00.pdf. Revised February 1, 2018. Accessed October 21, 2021.
Fajgenbaum DC. Novel insights and therapeutic approaches in idiopathic multicentric Castleman disease. Blood. 2018;132(22):2323-2330.
Fajgenbaum DC, Uldrick TS, Bagg A, et al. International, evidence-based consensus diagnostic criteria for HHV-8–negative/idiopathic multicentric Castleman disease. Blood. 2017;129(12):1646-1657.
Kaposi sarcoma. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/kaposi-sarcoma. Accessed October 21, 2021.
Kaposi sarcoma-associated herpesvirus. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/kaposi-sarcoma-associated-herpesvirus. Accessed October 21, 2021.
van Rhee F, Voorhees P, Dispenzieri A, et al. International, evidence-based consensus treatment guidelines for idiopathic multicentric Castleman disease. Blood. 2018;132(20):2115-2124.
Liu AY, Nabel CS, Finkelman BS, et al. Idiopathic multicentric Castleman’s disease: a systematic literature review. Lancet Haematol. 2016:3(4):e163-e175.
Night sweats. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/night-sweats. Accessed October 26, 2021.
Flu-like symptoms. National Cancer Institute. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/flu-like-symptoms. Accessed October 26, 2021.
Nishimura Y, Fajgenbaum DC, Pierson SK, et al. Validated international definition of the thrombocytopenia, anasarca, fever, reticulin fibrosis, renal insufficiency, and organomegaly clinical subtype (TAFRO) of idiopathic multicentric Castleman disease. Am J Hematol. 2021;96(10):1241-1252.
England JT, Abdulla A, Biggs CM, et al. Weathering the COVID-19 storm: lessons from hematologic cytokine syndromes. Blood Rev. 2021;45:100707.
van Rhee F, Stone K, Szmania S, Barlogie B, Singh Z. Castleman disease in the 21st century: an update on diagnosis, assessment, and therapy. Clin Adv Hematol Oncol. 2010;8(7):486-498.
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Your report
A diagnosis of idiopathic multicentric Castleman disease (iMCD) requires the presence of multiple swollen or enlarged lymph nodes. In some patients, the swollen lymph nodes may not be visible and may require imaging tests to confirm their presence. These symptoms alone are not enough to diagnose iMCD, as they could be signs of other diseases.
Talk to your doctor if you have any questions about this report.
Additional information about iMCD is available for healthcare professionals at KnowiMCD.com/HCP.
To protect your privacy, KnowiMCD.com does not save any of your information. Please be sure to download, save, and/or print this report.
Healthcare professionals can find information about the latest diagnostic criteria and treatment options by visiting
Your report
A diagnosis of idiopathic multicentric Castleman disease (iMCD) requires the presence of multiple swollen or enlarged lymph nodes. In some patients, the swollen lymph nodes may not be visible and may require imaging tests to confirm their presence. These symptoms alone are not enough to diagnose iMCD, as they could be signs of other diseases.
Talk to your doctor if you have any questions about this report.
Additional information about iMCD is available for healthcare professionals at KnowiMCD.com/HCP.
To protect your privacy, KnowiMCD.com does not save any of your information. Please be sure to download, save, and/or print this report.
Possible tests
In order to confirm a diagnosis of iMCD, a doctor will need to perform tests to detect the presence of multiple swollen lymph nodes.
- Physical examination
- Lab tests—blood or urine test
- Imaging tests—CT scan, x-ray, MRI, PET scan
- Excisional biopsy
By performing some of the above-mentioned tests, a doctor will be able to eliminate the possibility of autoimmune, cancerous, and infectious diseases. An excisional biopsy of the enlarged lymph node can confirm the diagnosis of iMCD.
The road to diagnosis
iMCD is a rare disease that can be difficult to diagnose because it can mimic so many other diseases. It may take a while to receive an accurate diagnosis because your doctor must rule out several different conditions before suspecting iMCD.
You may start your diagnosis journey at your primary care physician’s office, where you may be referred to a specialist.
Preparing for your appointment
Here are some tips to help you have a conversation with your doctor:
- Write down any symptoms you’ve experienced, even if they may seem unrelated
- Share the results of this Symptom Checker with your doctor
By performing some of the above-mentioned tests, a doctor will be able to eliminate the possibility of autoimmune, cancerous, and infectious diseases. An excisional biopsy of the enlarged lymph node can confirm the diagnosis of iMCD.
Start the conversation
Here are some tips to help you talk to your doctor about iMCD:
- What kinds of tests might I need to confirm iMCD?
- Do I need to plan for follow-up visits?
- What treatments are available for iMCD? How will they affect my life?
- Do you have any educational materials that I can take with me?
- What else do I need to know about iMCD?
Notes:
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Healthcare professionals can find information about the latest diagnostic criteria and treatment options by visiting
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Viral hemophagocytic lymphohistiocytosis.
A doctor who specializes in the branch of medicine that deals with rheumatic conditions.
Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes.
Positron emission tomography (PET) is a method of producing a 3-dimensional image of the internal structures of body tissues after administering a natural biochemical substance like glucose or fatty acids. These images are generated with the help of a computer.
A doctor who evaluates the changes caused by disease in tissues and body fluids and helps reach a diagnosis.
A doctor who specializes in the diagnosis and treatment of kidney abnormalities.
Macrophage activation syndrome.
Malignancy-associated hemophagocytic lymphohistiocytosis.
Lymph nodes make immune cells that help the body fight infection.
A key signaling molecule that helps to regulate the body’s immune system.
Infectious disease medicine is the subspecialty of internal medicine that focuses on diagnosing and managing infections.
A rare condition that affects multiple groups of lymph nodes throughout the body. Patients with iMCD are HIV negative and HHV-8 negative.
The underlying cause or origin of a disease is unknown.
Hemophagocytic lymphohistiocytosis.
Human immunodeficiency virus.
Human herpesvirus-8.
A doctor who specializes in the branch of medical science that deals with cancers of the blood and blood-forming tissues.
A procedure during which tissue is obtained from a swollen lymph node with the help of a fine needle and syringe.
During this surgical procedure, an incision/cut is made in the skin to remove a swollen lymph node, which is then examined under a microscope to look for signs of a disease. A small amount of healthy tissue around the abnormal area may also be removed.
Powerful molecules that are normally secreted by the cells of the immune system in response to infectious or noninfectious agents.
An overreaction of the body’s immune system in which too many cytokines are released into the bloodstream very quickly, with potentially severe or life-threatening effects.
Computed tomography (CT) is a method of producing an image of the internal structures by passing an x‑ray through the body.
The removal and examination of tissue, cells, or fluids from the body.
A condition in which the body’s immune system accidentally attacks itself.
Autoimmune lymphoproliferative syndrome.
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