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ICDO
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Castlemans
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Physicians Questions and Answers

This section is dedicated to questions and answers for the Castleman's Disease specialists located at various academic institutions. Information provided by the following medical professionals represent their own medical opinion and does not reflect or suggest that information provided is of the opinion or representation of the website or academic facility. The medical information is intended to be used as guidance and not as clinical direction or treatment. Consultation with your primary or treating physician is recommended and they may request to consult with one of our CD physicians who provide medical opinions on this site. For further direction, information or discussion on a particular opinion, please consult the physician directly and schedule a phone consult or a clinic visit.

Our Physicians:
Bart Barlogie, MD, PhD
Corey Casper, MD, MPH
Athanasios Fassas, MD
Nikhil Munshi , MD
Guido Tricot, MD, PhD
Frits van Rhee, MD, PhD, MRPC(UK) FRCPath

Bart Barlogie, MD, PhD Bart Barlogie, MD, was educated in Germany and earned his MD from Heidelberg University.  Following residency training at the Universities of Munich and Muenster, he joined the University of Texas MD Anderson Hospital and Tumor Research Institute in 1974 where he worked under Emil J Freireich and colleagues in Developmental Therapeutics.  Eventually, he served as Chairman of the Department of Hematology.  In 1989, he accepted the position of Director of Hematology/Oncology and Director of Research at the Arkansas Cancer Research Center, University of Arkansas for Medical Sciences.  In recognition of his institutional leadership role in myeloma, he was named the first Director of a newly established Myeloma and Transplantation Research Center and, later that year, he also became the Director of the Arkansas Cancer Research Center.  In 2001, Dr. Barlogie stepped down as the Director of the Arkansas Cancer Research Center to develop its Myeloma and Transplantation Research Center into the world’s first Myeloma Institute for Research and Therapy .

Corey Casper, MD, MPH University of Washington; Virology Research Clinic 600 Broadway, Suite 400; Seattle, WA 98122 Phone: (206) 720-4340, Fax: (206) 720-4371 Dr. Casper’s research projects involve the epidemiology, natural history, and treatment of infections with human herpesvirus 8 (also known as HHV-8, Kaposi’s sarcoma-associated herpesvirus, or KSHV)

Q. Finished my Rituxan & Dexamathasone treatments and my hair is falling out really bad. Is there anything I   can do to help my hair from falling out? I thought this treatment wouldn't cause hair loss.

A. Alopecia (hair falling out) is not a typical complication of either drug or CD. I would investigate other causes with a general practitioner.

Q. I saw my doctor today and she is curious. I told her I had seen something regarding brain tumors and CD. She asked me to see if I could find out the location of the tumors (hyopthalamus, pituatary etc.) so she can scan the right area. I have had a fever of unexplained origin for more than 3 years now and she thinks a hypothalamus tumor would possible explain that.

A. I have not heard of any connection, and can not think of a biologic link.


Q. The biopsy of the groin node showed "Castleman like tendencies" and they are going to take the node under the right armpit. The blood work was non-diagnostic. Is that normal with MCD?

A. CH50 is a test of "immune activity", typically used in the diagnosis and treatment of rheumatic disorders. The immune system uses a series of steps called the "complement cascade" to help optimize the work of antibodies. When the immune system is dysregulated, antibodies are often produced and consumed frequently, using up complement and lowering the CH50. This test typically is used for lupus, and has not been studied in CD. I would say that patients diagnosed with CD who have low CH50 should make sure they truly have CD and not lupus (I would want to see a negative double-stranded DNA test, and have the original biopsy re-reviewed by an expert pathologist). If lupus is ruled out, than I would say that a low CH50 probably just represents immune dysregulation that accompanies CD and argue for aggressive treatment of CD.


Q. Is there any link between Castleman's Disease and Human Papilloma Virus (HPV) ?  

A. No. Only human herpesvirus 8 (HHV-8) has been associated with CD, as reviewed in my recent article:

The aetiology and management of Castleman disease at 50 years: translating pathophysiology to patient care

Q. Any new theories, news, etc. on what causes this disease? I wondered if all of the new DX of folks out there and increased awareness has brought any common denominators present? I keep wondering if years ago before my MCD diagnosis (dx) a bad bout with flu or something similar that lasted a long time but never showed positive for mono or anything may have something to do with it?

A. CD is due to the unregulated growth of a type of a specific type of immune cell, known as the B-lymphocyte. These cells typically are responsible for coordinating the immune response against infections and producing antibodies. In CD, there are too many that are called to the lymph node, and they abnormally produce signals that rev up other cells and the immune system to inflame.

In my opinion, two things can cause this. First, infection with a virus can cause B-cells to respond. A relatively new virus, human herpesvirus 8 (very similar to Epstein barr virus) has been shown to cause between 40-100% of CD cases, probably more multicentric than unicentric. The virus makes a copy of one of the molecules cells use to communicate and rev up the immune system (interleukin 6).

Among the persons who are not infected with HHV-8, they may have been born with problems in how the body regulates and produces interleukin 6. This is being increasingly described in the medical literature.

In sum, interleukin 6 production is key to the development of CD. We have much more to learn, but this is a good start.

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Athanasios Fassas, MD Assistant Professor, Myeloma Institute for Research and Therapy University of Arkansas for Medical Sciences Myeloma Institute for Research and Therapy Little Rock, AR

Q. Does CD have anything to do with seizures? Does a person have CD for the rest of his/her life after having been diagnosed -is he/she in remission when nothing is showing up? Is it a form of cancer?

A. Seizures have been reported with CD. Although technically not a cancer, it may behave in a very "malignant" way. CD may recur at any time. Periodic follow-up, as dictated by common sense and symptomatology, is therefore indicated.
 

Q. My most recent pathology report which was reviewed by 3 hematopathologists at JHH hospital didn't confirm that I have Castleman's. The diagnosis I received this time is "Reactive Paracortical Hyperlasia". The last biopsy on the nodes removed from by abdominal area revealed a Castleman's diagnosis. By report, the heterogenous mixture of CD4-positive and CD8-positive cells that also demonstrate expression of CD5 and CD7. An immunostain for HHV-8 is reportedly negative. In addition, there is no abnormal increase in paracortical vascularity. Overall, these findings represent non-specific paracortical hyperplasia. There is no definitive evidence of Castleman's disease, and there is no evidence of lymphoma. What is the medical interpretation of these results?

A. If (s)he had multiple biopsies of lymph nodes, it would be prudent to have them reviewed by hematopathologists for a definite diagnosis. Then (s)he should consult with a clinician concerning the practical relevance of the diagnosis.
 

Q. Patient received a diagnosis of Castleman's disease based on the lymph node biopsy after receiving CHOP chemotherapy for Non Hodgkin's Lymphoma. Through my search for a treatment and re-staging of the disease we found the following; Castleman's diagnosis must NOT be done for the first time after any chemotherapy treatment as the recommendations of MD Anderson; the lymph node structure in a Non Hodgkin's lymphoma may be changed to give a picture similar to the Castleman's disease after necrosis and destruction by the chemotherapy. I sent the specimens to another clinician order to reclassify it again, so, the Dx was reclassified as Non Hodgkin's Lymphoma again and the patient is receiving treatment for it now. Anti CD20 monoclonal antibodies are now available under the name "Rituxan, Rituxin or Rituximab" with excellent results for CD20 positive lymphoplasmacytiod B cell lymphoma. I would like to draw your attentions that Castleman's MAY be complicated by lymphoma but the misdiagnosis in these cases is easy since it may be partially treated as lymphoma without a coexisting Castleman's. Any in put from academia?

A. This confirms the notion of establishing a diagnosis before treatment, a statement applicable in all fields of medicine. Chances are that only one (the same) diagnosis of lymphoma was present at all times

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Nikhil Munshi , MD Associate Director Jerome Lipper Myeloma Center Dana Farber Cancer Institute 44 Binney Street, Boston, MA 02115 (617) 632-5607  -  (617) 632-4862 Fax

Dr. Munshi received his MD from the SSG Hospital and the MS University of Baroda, India, in 1984. He completed a research fellowship in medical oncology at the Johns Hopkins Oncology Center in 1987, and a clinical fellowship in hematology-oncology at the Indiana University Medical Center in 1990. In 2001 he joined DFCI, where he focuses on basic laboratory and translational research on immunotherapy in multiple myeloma.

Q. Can unicentric/localized CD develop into multicentric/widespread CD? Can unicentric/localized CD recur after resection? Will a CD mass keep growing if not resected?  

A. I would like to give a general out line of how Castleman's may evolve by answering some of the very interesting questions that have been asked.


Q. Can unicentric/localized CD develop into multicentric/widespread CD?

A. Unicentric Castleman's (CD) is a disease localized to one lymph area and is essentially resectable by surgery. However, an apparent Unicentric Castleman's can later be diagnosed as multicentric. This is specially true for plasma cell variant which more often is multicentric.


Q. Can unicentric/localized CD recur after resection?

A. Hyaline vascular type rarely recurs if it presents as localized disease and is completely resected. (I have seen recurrence in one patient). However the question remains if it was really multicentric when resected but the other lesions were too small to be seen. Plasma cell variant may recur much more often.


Q. Will a CD mass keep growing if not resected? ie, you have a solitary mass diagnosed as CD. If it's not surgically resected or medically treated, can CD pop up later somewhere else in the body? Will the mass keep growing?

A. Yes it can keep on growing. Also sometimes it may decrease in size a little bit and then increase again; possible related with cytokine changes.


Q. Or, if a unicentric CD is treated and completely resected, can CD still pop up somewhere else?

A. Yes


Q. Can CD recur at the same place it was before (recur at the site of resection) or are you totally cured? i've heard you are cured after resection, but is it possible for CD to come back after supposedly curative resection?

A. Hyaline vascular type rarely recurs if completely resected. However plasma cell variant may recur much more often and possibly at the site of prior resection or elsewhere.


Q. In other words, does multicentric CD start as unicentric CD? Will taking out the first mass prevent others from forming?

A. Not necessarily but we do not know much about this aspect of the biology of the disease.


Q. What is the natural progression for this disease, whether it be unicentric or multicentric?

A. The above answers addresses this question.


Q. One last question, if a unicentric CD is surgically removed, what kind of follow up is required?

A. I've heard a CT should be done within the next 5 years. This implies that unicentric CD may not be completely cured by surgical resection.


Q. What do you think?

A. A patient with complete resection of unicentric CD requires frequent follow up visits including IL-6 and CRP measurements and depending on the site of initial lymph nodes, a CT scan initially 6 monthly and later on yearly and if stable for 2-3 years then less frequently.


Q. Patient received a diagnosis of Castleman's disease based on the lymph node biopsy after receiving CHOP chemotherapy for Non Hodgkin's Lymphoma. Through my search for a treatment and re-staging of the disease we found the following; Castleman's diagnosis must NOT be done for the first time after any chemotherapy treatment as the recommendations of MD Anderson; the lymph node structure in a Non Hodgkin's lymphoma may be changed to give a picture similar to the Castleman's disease after necrosis and destruction by the chemotherapy. I sent the specimens to another clinician order to reclassify it again, so, the Dx was reclassified as Non Hodgkin's Lymphoma again and the patient is receiving treatment for it now. Anti CD20 monoclonal antibodies are now available under the name "Rituxan, Rituxin or Rituximab" with excellent results for CD20 positive lymphoplasmacytiod B cell lymphoma. I would like to draw your attentions that Castleman's MAY be complicated by lymphoma but the misdiagnosis in these cases is easy since it may be partially treated as lymphoma without a coexisting Castleman's. Any in put from academia?

A. Any condition including Castleman's and Non-Hodgkin's Lymphoma can be misdiagnosed after chemotherapy. So one has to be careful in evaluating biopsies if they were done too close to therapy. A classic case of Castleman is not associated with lymphoma, however both the diseases can be misdiagnosed and one has to be careful in evaluating the biopsies. I would not call it reclassification of Castleman.
 

Q. Female patient has the plasma cell variant of CD, received 8 weeks of Rituxan and steroid treatments with minimal results. On June 2nd, had the effected lymph nodes removed from the mesentery. The last 3 PET scans indicated suspicious activity in the area of the endometrial cavity. Before surgery, an OB/GYN was consulted. who did an endometrial biopsy. It came back normal. The post surgery PET indicated the area was larger and the SUV had risen from 4 to 5.6. The first PET that picked it up had an SUV of 1.7. Patient returned to the OB/GYN where an ultrasound was performed. This, too, was normal. The OB/GYN stated that what ever it is isn't in the uterus. The question is--could this just be normal hormonal activity? The only thing that concerns the patient is that it's in the same location on each PET scan and it's grown in intensity. The scans have been done during different times of my cycle. CT scans have revealed nothing in that area.

A. There are to part to the question. The patient's question about the relation between cycle and PET scan -The menstrual cycle does change PET results. To quote one article in a medical journal "In women of reproductive age, 18F-FDG imaging should preferably be done within a week before or a few days after the
menstrual flow phase to avoid any misinterpretation of pelvic 18F-FDG PET images". So she needs to have scan at specific time.
 
Regarding follow up she should get, besides getting CT and/or PET, she should get the standard biochemical measurements which in plasmacytic variant is important. The evaluations should be a combined interpretation of all including clinical exams and symptoms.

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Guido Tricot, MD, PhD Director of Clinical Research University of Arkansas for Medical Sciences Myeloma Institute for Research and Therapy Little Rock, AR Phone: 501-686-8250; Fax: 501-686-6442

Guido Tricot, MD, PhD, is a Professor of Medicine and Pathology at the University of Arkansas for Medical Sciences (UAMS), and Director of Clinical Research  at the Myeloma Institute for Research and Therapy.  Dr. Tricot was formerly on staff at UAMS as Director of Experimental Therapeutics with the myeloma program from 1993 to 1997.  Prior to returning to UAMS in 2000, he served as Director of the Bone Marrow and Stem Cell Transplant Program at the University of Maryland in Baltimore.  Dr. Tricot oversees clinical and research activities of the Myeloma Institute for Research and Therapy and is integrally involved in the management of a $13.2 million grant from the National Cancer Institute that is being applied to unraveling the biology of myeloma and developing curative therapy.

Q.  The IU doctors decided to put me on a round of Prednisone therapy, starting with 2 weeks at 100 MG and then tapering off. This is the end of day nine/beginning of day ten. Even with the Ambien, sleep eludes me. When it does come, it comes in fits and I wake frequently, never feeling quite rested. Being this my first time on this high of a dose of steroid I wanted to ask how often/frequent have some of you endured these rounds? What real benefits have been noted? Did the reduction of the size of the lymph nodes help reduce the other symptoms?

A.  The high dose of steroids needs to be taken as early in the morning as       possible.The high dose steroids should relieve the symptoms and there  may be some shrinking of the lymph nodes, but usually not a lot.


Q. I just got my CT results back and after 2 rounds (8 total infusions) of Rituxan along with the Dexamathasone no decrease in size. We did wait a month after the last one for the Rituxan to have time to work. Do you know if this Rituxan really works for Castleman's? I also have heel pain/joint pain. Any correlation?
 
A. Rituxan clearly works in a portion of patients with CD and is easy to tolerate. Its effect is mainly on the symptoms accompanying the disease rather than on shrinking the nodes. If you have nodes but no symptoms and if the nodes do not endanger the function of any organ, surgery is the treatment of choice. If not possible, a wait and see approach with careful follow up is probably best. If you have symptoms and these do not respond to the Rituxan, you need to be treated differently.
 

Q. Do all Castleman's patients have abnormal levels of IL-6?

A. No. the IL-6 levels usually but not always correlate with the gravity of the symptoms CD patients have.
 

Q. I have calcified lymphnodes. Does anyone else have this? Could it be related to Castleman's or do you think its from an infection?

A. The calcified lymph nodes are unlikely related to CD. The most likely explanation is an old infection, such as Histoplasma or Tb.
 

Q. My CT Scan showed a lesion on my liver and the head of my pancreas. Has anyone had lesions show up in these areas? I was told by my nurse that it was not lymph nodes. Could this still be connected to Castleman's?

A. I think that this patient needs to have a biopsy of either the liver or the pancreas lesion. Although it may be CD, I would not believe that without a biopsy.
 

Q. I saw my doctor today and she is curious. I told her I had seen something regarding brain tumors and CD. She asked me to see if I could find out the location of the tumors (hyopthalamus, pituatary etc.) so she can scan the right area. I have had a fever of unexplained origin for more than 3 years now and she thinks a hypothalamus tumor would possible explain that.

A. Lymphoma lymph nodes can be blue as well as CD lymph nodes. We will have to wait for the results of the biopsies.
 

Q. One year ago I went to my GP for a physical and I was diagnosed in December 2004 with HV Castleman's disease after having a mass removed from my neck. I just had my 6 month CT scan which showed everything stable but on the pelvic CT it showed bilateral adnexal cysts so I just saw my gynecologist and he sent me for a pelvic ultrasound - preliminary results showed a complex cyst on my right ovary and a solid echogenic mass as well as a simple cyst on my left ovary -this needs to explored further probably removing it. Would this have anything at all to do with the Castleman's disease?

A. It seems rather unlikely, but everything is possible with CD. 
 

Q. I just had a biopsy and instead of taking just the one lymph node from under the arm (which was not as big as the one previously removed from the groin), the doctor removed two other nodes because they were blue . Has anyone heard of this? Is there any significance?

A. Lymphoma lymph nodes can be blue as well as CD lymph nodes. We will       have to wait for the results of the biopsies.


Q. Now that I have the mass removed I'm still not in the clear. The doctor is talking about putting me on prednisone. I have a positive ANA my doctor doesn't think that is related with Castleman's. His biggest concern is lymphoma. I'm not sure what a positive ANA means.

ANA Reference: http://206.161.82.9/education/articles/ana.html

A. I would not be surprised that CD patients would have a higher frequency of auto-immune diseases and that the two were linked.
 

Q. I had an inguinal mass removed. Dx'd as HVCD. I have recently found another enlarged node in the same area. My question is for CD to be multicentric, does more than one node need to be affected at the same time, or does a reoccurrence change it from localized to multicentric?

A. Multicentric means more than one lymph node area is involved. If a recurrence occurs in the same lymph node area it is not considered multicentric.


Q.  Is there a link between Castleman's Disease and Lymphoma?

A. Some CD patients evolve to Myeloma or lymphoma.

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Frits van Rhee, MD, PhD, MRPC(UK) FRCPath Director of Immunotherapy and Allogeneic Transplantation University of Arkansas for Medical Sciences Myeloma Institute for Research and Therapy Little Rock, AR

Q. Now that I have the mass removed I'm still not in the clear. The doctor is talking about putting me on prednisone. I have a positive ANA my doctor doesn't think that is related with Castleman's. His biggest concern is lymphoma. I'm not sure what a positive ANA means.

ANA Reference: http://206.161.82.9/education/articles/ana.html

A. Many patients with CD have a positive ANA due to immune dysregulation. I check for it routinely and find it. A positive ANA does not necessarily mean clinical auto-immune disease although this can occur of course.
 

Q. For patients who have had Rituxan therapy, how long did it take to see any kind of improvement. Also, did anyone also have POEMS; and, if so, did those symptoms improve, worsen, or stay the same?

A. If this is Rituxan with steroids then we should expect to see an improvement certainly after 4 doses. This may not yet be a complete response!!!!! Depending on the bulk of the disease 4 doses are not enough. In my experience usually at least 8 doses are required. I give four and reassess response and the need for more doses.

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