Lymphoma Rounds: In the box
Should doctors think in the box? Sure, if the box works, If the therapy is effective, if the criteria for diagnosis define an entity for which the treatment is successful, barring a complicating factor, then one should follow the guidelines, the textbook. . One should be sure about identifying the problem and choose the best solution and do it.There are situations in which this scenario applies: many infections, most Hodgkin's Lymphomas, many testicular cancers. Once the diagnosis is secured, the exceptions ruled out, and the patient tolerance assured, following the formula will yield the desired outcome.
I went to lymphoma rounds. The first case was a case of lymphomatoid granulomatosis. This is an unusual diagnosis. The case was more unusual because of CNS signs and symptoms. The case was presented by a fellow and discussed by a neuro-oncologist. That meant that the neurological aspects o the case were made primary.
The relationship to Epstein-Barr virus in this lymphoma was clearly stated and recognized. We had all learned the pathophysiology of EBV disease: cells are transformed, changed by EBV into cells that share many qualities with malignant cancer cells. They are immortal, The program for cell death is turned off..They reproduce out of control.
The acute disease, mononucleosis, usually comes to a good conclusion withe the patient's T cell based immunity victorious. But there are EBV driven lymphomas that are not self limited, lymphomas that do not improve without strong, chemotherapeutic intervention. These include various lymphomas in the immunocomprimised. Patients with (uncontrolled) HIV disease can get aggressive lymphomas, including CNS lymphomas, from EBV. One of the most aggressive of all lymphomas, Burkitts lymphoma, in its classical form, is an EBV driven disease. Patients who have had organ transplants and take immunosuppression can get less aggressive lymphomas like PTLD, a lymphoma that often responds to changes in immunosuppresion. EBV disease often has an immunological basis
The case was discussed in terms of published treatment outcomes, the standard therapy was CHOP, all purpose lymphoma therapy. Some mention was made of interferon, which seemed to succeed in some cases, but was not used in this case.
I asked if the this entity could be divided into different groups based upon the immunologic status of the patient, and the nature of the cells identified in the biopsies. After a long silence, I said that I did not expect and answer to the question. (This patient's immunologic status had not been investigated.)
The true meaning of the question involved the approach to such diseases. We live in an era of instant access to millions of research findings. Almost anything you can think of has been written about, What is written is not necessarily good, and may even be misleading, but should not be ignored.
When a disease is outside the of the set of the clearly curable with standard approaches, the consideration should include an approach that incorporates our beliefs about pathophysiology. Such an approach can lead to other pathways for diagnosis, treatment and prognosis.
I think that there is always an immunological aspect to EBV disease. The immunologic aspect has implications for HIV related lymphoma, encouraging anti retrovirals and the reconstitution of CD4 mediated immunity. We exploit it in PTLD by adjusting immunosuppression ( sometimes along with Rituxan) Even when there is central nervous system involvement, simply reducing immunosuppression can be sufficient for remission in PTLD.
I do not completely trust our (current) understanding of pathophysiology. It will probably change with the acquisition of further knowledge, but I am not prepared to take it out of the picture,
Hypotheses about the nature of the patient's disease can be lifesaving. They can also be terribly misleading. Interpretation requires great care and open discussion
Should doctors think in the box? Sure, if the box works, If the therapy is effective, if the criteria for diagnosis define an entity for which the treatment is successful, barring a complicating factor, then one should follow the guidelines, the textbook. . One should be sure about identifying the problem and choose the best solution and do it.There are situations in which this scenario applies: many infections, most Hodgkin's Lymphomas, many testicular cancers. Once the diagnosis is secured, the exceptions ruled out, and the patient tolerance assured, following the formula will yield the desired outcome.
I went to lymphoma rounds. The first case was a case of lymphomatoid granulomatosis. This is an unusual diagnosis. The case was more unusual because of CNS signs and symptoms. The case was presented by a fellow and discussed by a neuro-oncologist. That meant that the neurological aspects o the case were made primary.
The relationship to Epstein-Barr virus in this lymphoma was clearly stated and recognized. We had all learned the pathophysiology of EBV disease: cells are transformed, changed by EBV into cells that share many qualities with malignant cancer cells. They are immortal, The program for cell death is turned off..They reproduce out of control.
The acute disease, mononucleosis, usually comes to a good conclusion withe the patient's T cell based immunity victorious. But there are EBV driven lymphomas that are not self limited, lymphomas that do not improve without strong, chemotherapeutic intervention. These include various lymphomas in the immunocomprimised. Patients with (uncontrolled) HIV disease can get aggressive lymphomas, including CNS lymphomas, from EBV. One of the most aggressive of all lymphomas, Burkitts lymphoma, in its classical form, is an EBV driven disease. Patients who have had organ transplants and take immunosuppression can get less aggressive lymphomas like PTLD, a lymphoma that often responds to changes in immunosuppresion. EBV disease often has an immunological basis
The case was discussed in terms of published treatment outcomes, the standard therapy was CHOP, all purpose lymphoma therapy. Some mention was made of interferon, which seemed to succeed in some cases, but was not used in this case.
I asked if the this entity could be divided into different groups based upon the immunologic status of the patient, and the nature of the cells identified in the biopsies. After a long silence, I said that I did not expect and answer to the question. (This patient's immunologic status had not been investigated.)
The true meaning of the question involved the approach to such diseases. We live in an era of instant access to millions of research findings. Almost anything you can think of has been written about, What is written is not necessarily good, and may even be misleading, but should not be ignored.
When a disease is outside the of the set of the clearly curable with standard approaches, the consideration should include an approach that incorporates our beliefs about pathophysiology. Such an approach can lead to other pathways for diagnosis, treatment and prognosis.
I think that there is always an immunological aspect to EBV disease. The immunologic aspect has implications for HIV related lymphoma, encouraging anti retrovirals and the reconstitution of CD4 mediated immunity. We exploit it in PTLD by adjusting immunosuppression ( sometimes along with Rituxan) Even when there is central nervous system involvement, simply reducing immunosuppression can be sufficient for remission in PTLD.
I do not completely trust our (current) understanding of pathophysiology. It will probably change with the acquisition of further knowledge, but I am not prepared to take it out of the picture,
Hypotheses about the nature of the patient's disease can be lifesaving. They can also be terribly misleading. Interpretation requires great care and open discussion
