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Holzheimer RG, Mannick JA, editors. Surgical Treatment: Evidence-Based and Problem-Oriented. Munich: Zuckschwerdt; 2001.

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Surgical Treatment: Evidence-Based and Problem-Oriented.

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, M.D.

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The management of both Hodgkin's and non-Hodgkin's lymphomas has changed significantly over the past 25 years. Primarily due to advances in radiation therapy and chemotherapy, the majority of patients now diagnosed with one of these malignancies will survive, a truly remarkable accomplishment given their inevitably fatal outcome at the advent of twentieth century. Over this same time, the role of surgery has also been in transition. In this chapter, we will highlight some of these important changes, especially how surgery has evolved to play a more limited role in the staging and treatment of the disease. The management of extranodal lymphomas, such as gastric lymphoma, will not be discussed here, as it is covered in more detail in accompanying chapters.

Epidemiology and pathology

The incidence of Hodgkin's lymphoma varies in different parts of the world, yet within each country or region evaluated, the incidence has remained remarkably stable over the past 20 years. In the case of non-Hodgkin's lymphomas, however, the incidence has been progressively increasing over time world-wide. In fact, in many countries, the incidence of non-Hodgkin's lymphoma nearly doubled between 1970 and 1985. For both Hodgkin's disease and non-Hodgkin's lymphoma, the highest incidence rates are found in developed countries (12). The reason for this regional difference is largely unknown.

A unified and comprehensive classification system for lymphomas has recently been devised by an international group to reconcile the often disparate Working Formulation and Kiel Classification systems that were used predominantly in the United States and Europe, respectively. In addition, the new classification scheme included several recently recognized forms of non-Hodgkin's lymphomas. The newly proposed system, the revised European-American classification of lymphoid neoplasms (-REAL), has been shown to be clinically applicable in a retrospective study of over 1300 patients (3). The classification of Hodgkin's disease is largely unchanged under this new scheme (see table I). It should be noted that the REAL classification system makes no specific attempt to group the various diagnoses by overall prognosis, as was the case in previous systems.

Table I. The Revised European-American Lymphoma Classification.

Table I

The Revised European-American Lymphoma Classification.

Surgery in the diagnosis of lymphoma

The diagnosis of lymphoma has traditionally required a tissue sample for complete histopathologic characterization and classification. This need for adequate tissue has been heightened due to the genetic and molecular phenotyping that are now routinely performed as a part of the pathologic diagnosis. When possible, a whole lymph node should be biopsied. In those patients with palpable peripheral lymphadenopathy, an open excisional biopsy is performed, avoiding inguinal lymph nodes if equally suspicious adenopathy is present elsewhere.

A common situation, however, is one in which a patient will present without peripheral lymphadenopathy but will have enlarged intrathoracic, intraabdominal or retroperitoneal lymph nodes which would be poorly amenable to a simple open biopsy. As with many areas of medicine, however, efforts have been made to identify less invasive means of obtaining tissue for a diagnosis. Several recent, retrospective reports have confirmed that image-guided core-needle biopsy provided sufficient tissue to make a specific diagnosis of Hodgkin's disease or non-Hodgkin's lymphoma in 83% to 86% of cases. Those patients who had an inconclusive core-needle biopsy required subsequent open biopsy (4). In both series, a significant number of those patients in whom a core-needle biopsy provided sufficient tissue were those in which a diagnosis of lymphoma had previously been established. Patients who underwent core-needle biopsy for a first time diagnosis of lymphoma were more likely to have inconclusive or unsuccessful biopsies and subsequently require an open biopsy. Fine-needle aspiration (FNA) of suspicious lymph nodes will not provide adequate tissue for the definitive diagnosis of lymphoma. In conjunction with flow cytometry, cytologic specimens obtained by FNA may be useful in differentiating between reactive lymphoid hyperplasia and malignant lymphoproliferative disease, as populations of reactive lymphocytes would be polyclonal in origin, while those from a lymphoma would be monoclonal.

If the core-needle biopsy specimen is inadequate for an accurate diagnosis, minimally invasive surgical techniques, such as thoracoscopy or laparoscopy, are the preferred means for obtaining more tissue. A number of series have reported that laparoscopy was successful in obtaining diagnostic tissue in 78–84% of patients with minimal morbidity and no mortality (5). Only in cases where minimally invasive techniques are unsuccessful or deemed to be technically difficult or unsafe should an open laparotomy or thoracotomy be performed.

In all cases, the handling and distribution of the tissue samples to the appropriate laboratories should be directly overseen by the operating surgeon. Samples should be submitted to the pathologist fresh and not in formalin or other preservatives. In the case of biopsies performed by laparoscopy or thoracoscopy, a portion of the tissue should be taken to pathology for frozen section analysis to confirm that the tissue removed is, indeed, diagnostic for an abnormal lymphoid process prior to the conclusion of the case.

Staging laparotomy in Hodgkin's disease

Traditionally, a staging laparotomy was a standard part of the evaluation of patients with early stage Hodgkin's disease, as it was the best method to distinguish those patients who had limited disease (disease confined to above the diaphragm) from those with more extensive involvement (disease both above and below the diaphragm, involvement of extranodal sites). In fact, staging laparotomy remains the single most reliable means of distinguishing these two populations. Current imaging techniques, such as computed tomography or lymphangiography, are hampered by their low sensitivity and specificity in detecting involved abdominal lymph nodes, spleen and liver (6). In patients staged clinically to have Hodgkin's disease confined to above the diaphragm, 20% to 35% will have occult splenic or upper abdominal lymph node involvement at the time of staging laparotomy. Conversely, 32% to 55% of patients clinically staged as having disease on both sides of the diaphragm will be downstaged with a laparotomy demonstrating no infradiaphragmatic involvement.

The importance of the staging laparotomy in the management of Hodgkin's disease has decreased over the past decade, but remains an area of controversy. The value of the additional information gained from a staging laparotomy must be measured by its importance in altering the treatment and, ultimately, the survival of the disease. At issue in the controversy is whether treatment that is specifically adapted to the pathologic stage confers an advantage over treatment that is governed by clinical findings and prognostic factors. The European Organization for Research and Treatment of Cancer (EORTC) Lymphoma Cooperative group has systematically examined this question in a well-planned series of randomized, prospective studies. The results from these trials demonstrated that the relapse-free survival was worse in patients who were treated based on only clinical staging. Due to the success of salvage chemotherapy, however, there was no such decrement in the overall survival in this treatment group. In fact, the group that was clinically staged had a better survival than those subjected to laparotomy, primarily due to operative mortality in the latter group (7). Thus, it may not be crucial to accurately stage most patients with a laparotomy, as radiation therapy, chemotherapy, or a combination of both will effectively treat the majority of patients with early stage Hodgkin's disease, and recurrent disease can be successfully treated with salvage chemotherapy without a decrease in overall survival.

Proponents of the staging laparotomy argue that adaptive treatment regimens, although not associated with a survival advantage, may be associated with a lower incidence of long-term treatment related morbidity. As more patients with Hodgkin's disease live longer, it is evident that these patients are at an increased risk for second primary cancers, such as leukemias, non-Hodgkin's lymphomas and solid malignancies, which may be attributed to previous exposure to chemotherapy, radiation therapy or a combination of the two (8, 9). Hence, minimizing the amount and number of treatments patients are given could potentially reduce the incidence of these late complications. This has yet to be proven in any prospective, randomized trials specifically addressing this issue.

Splenectomy in Non-Hodgkin's lymphoma

Splenectomy appears to play a role in the treatment of non-Hodgkin's lymphoma, especially for palliation of the symptoms of splenomegaly and the sequelae of hypersplenism. Primary splenic lymphoma is a rare entity, and in these cases, splenectomy has been reported to be curative. There is little evidence, however, that splenectomy can confer any survival advantage when used in settings other than this very localized disease. Similarly, there is a paucity of data to support the concept of surgical debulking of disease in the treatment of lymphoma.

Data supporting splenectomy in the palliative setting come from small, retrospective series. One of the most common indications for splenectomy in non-Hodgkin's lymphoma is the palliation of symptoms, such as left upper quadrant pain, early satiety, weakness and fatigue, that accompany the marked splenomegaly often seen in this disease. Another common indication for splenectomy is for the treatment of cytopenias resulting from hypersplenism. The data from most series indicate that splenectomy is successful in relieving anemia, thrombocytopenia or leukopenia in 50% to 94% of cases. Response rates appear to be best when splenectomy is performed before the spleen becomes massively enlarged or before the patient experiences severe or life-threatening symptoms from their cytopenia or from the progression of their lymphomatous process.

Residual splenomegaly in a patient who has otherwise successfully responded in other sites following chemotherapy for lymphoma is another reason for performing a splenectomy. In these cases, the procedure may be performed for both diagnostic and therapeutic reasons; it can determine if the splenomegaly is due to persistent lymphoma, and should this be true, it can potentially eliminate the focus of residual disease. A less common indication for splenectomy that may be seen more frequently in the future is to allow patients to become eligible for enrollment onto novel treatment protocols. An example of this is in patients with lymphoma refractory to conventional chemotherapy who were treated with radioimmunotherapy using a radiolabelled anti-CD20 antibody. In some of these patients, splenomegaly was found to complicate treatment, as the large organ served as an “antigen sink”, effectively decreasing the dose of radionuclide available to treat other sites of disease. Thus, pretreatment splenectomy may be indicated to eliminate this complicating factor (10).


The continued refinement of radiation therapy and chemotherapy for the treatment of both Hodgkin's disease and non-Hodgkin's lymphomas have resulted in a greater number of cures with fewer treatment-related complications. The role of surgery in the management of these malignancies has become more peripheral, and is most often called upon for diagnosis rather than therapy. Prospective trials have demonstrated little benefit to staging laparotomy in Hodgkin's disease, as adapted treatment based on the pathologic result does not translate into an improved overall survival. Furthermore, in non-Hodgkin's lymphoma, splenectomy is used more for palliation and has little role in therapy. Only in rare cases of primary splenic lymphoma can splenectomy be viewed as a primary therapy, however, whether additional adjuvant chemotherapy or radiation is necessary has not been evaluated.


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Copyright © 2001, W. Zuckschwerdt Verlag GmbH.
Bookshelf ID: NBK6941


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