Abdominal lymphoma: Lack of complete surgical staging

Abdominal Lymphoma: Lack of Complete Surgical Staging

Sharon Ondreyco, MD, Salt Lake City, Utah Harmon J. Eyre, MD, Salt Lake City, Utah Carl Kjeldsberg, MD, Salt Lake City, Utah William 1. Sause, MD, Salt Lake City, Utah

Since the introduction of Rappaport’s histologic classification of non-Hodgkin’s lymphomas in 1966, much has been learned about the natural history of these diseases [I 21. The histologic type of lymphoma is prognostically important [2]. “Favorable” types include diffuse well-differentiated lymphocytic lymphoma, nodular poorly differentiated lymphocytic lymphoma, and nodular mixed lymphoma. Patients with these types have a relatively good prognosis and can survive for many years without treatment [3]. Lymphomas of “unfavorable” histology include diffuse histiocytic lymphoma, diffuse poorly differentiated lymphocytic lymphoma, and undifferentiated lymphoma. Patients with these types have a short survival without aggressive therapy. With the introduction of combination chemotherapy in the treatment of lymphomas of unfavorable histology, complete response rates approach 80 percent and many patients are potentially curable

11941. In addition to the histologic classification, the extent of disease is also a significant prognostic factor. Several series have shown a correlation between the stage of disease and survival [5,6]. Clinical staging has been shown to be inaccurate in non-Hodgkin’s lymphomas [7,8]. Goffinet et al [8] advanced the stage of 31 percent of patients after laparotomy. At surgery, unsuspected disease was most often found in the spleen, liver, bone marrow, and intraabdominal lymph nodes. Determining the histologic type and careful staging of the disease has led to a better understanding of lymphomas as well as better treatment planning and improved prognosis. Unfortunately, accurate staging of abdominal lymphomas rarely occurs [S-13]. Without accurate staging, it is impossible to correlate the histologic From the Departments of Medicine, Pathology, and Radiology, University of Utah Collage of Medicine. Salt Lake City, Utah. Supported in part by Grant CA 18013 from the National Institutes of Health, Bethesda, Maryland, and a Clinical Fellowship Grant from the American Cancer Society, New York, New York. Requests for reprints should be addressed to tin J. Eyre, MD, Division of Hematology/Oncology. 50 North Medical Drive, Salt Lake City, Utah 84132.

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type or the method of treatment with the outcome. As a result, no uniform recommendations can be made regarding optimal treatment for abdominal lymphomas. To assess the magnitude of the problem and emphasize the need for accurate staging at the time of initial laparotomy, we reviewed all patients with primary abdominal lymphomas seen over a 10 year period at the University of Utah. Materisil and Methods

Criteria for inclusion in the study required that the initial diagnosis was made at the time of laparotomy, that the patients were seen at the University of Utah at some time during their initial evaluation and treatment, and that their charts, operative reports, and pathologic material were available for review. Thirty-nine cases of lymphoma presenting as primary abdominal disease were reviewed. Six cases were excluded because of inadequate data. The 33 other patients form the basis of this report. Patients were staged according to the Ann Arbor staging classification [14] based on their physical examination, radiologic studies, operative reports, and biopsy material. We defined adequate surgical staging as follows: (1) description of the primary tumor with respect to site of origin, size, and extension to other organs; (2) biopsy of the primary tumor; (3) defining with metal clips the margins of unresectable tumor or the tumor bed if the tumor was resected; (4) biopsy of regional lymph nodes; (5) biopsy of abnormal appearing lymph nodes; (6) biopsy of selected nodal groups not clinically involved (mesenteric, paraaortic, iliac node groups); (7) biopsy and description of the liver with respect to size, consistency, and appearance; (8) splenectomy if possible; if not possible then examination of the spleen with respect to its size and appearance; and (9) bone marrow biopsy. Results Clinical findings: The characteristics of the 33 patients in the study are recorded in Table I. Our patients were predominantly over age 50 years (mean 57). The sex ratio was 1 to 1. The distribution according to primary site of disease was similar to that in other studies [11,13]. The most common presenting symptoms were abdominal pain, weight loss, fatigue, nausea, and

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Surgical Staging in Abdominal

TABLE I

Lymphoma

Patient Charade&tics Primary Site

Patients (n) Age range Mean age (years) Sex ratio (M:F)

Stomach

Small Bowel

Large Bowel

Mesentery

Retroperitoneum (Pancreas, Nodes)

Spleen

9 32-76 56 4:5

6 25-72 56 51

2 26-50 38 1:l

4 62-81 68.5 1:3

9 56-68 63 4:5

3 56-68 62 2:l

Radiologic data: One or more abdominal radiographic studies were performed before laparotomy in 24 of the patients (Table IV). The most consistently helpful study was the upper gastrointestinal series in gastric lymphoma. In 10 of 12 instances where abdominal ultrasound or computed tomography was performed, the studies were abnormal. Intravenous pyelography was the least informative preoperative test, with positive findings in only 3 of 10 studies. Pathologic data: The pathologic findings in each case were reviewed and described according to Rappaport’s histologic classification 1151 (Table V). One patient was found to have mixed cellularity Hodgkin’s disease but was included because he was

vomiting (Table II). The presenting symptoms were similar regardless of the primary site of disease and were similar to those described in other series [I 1,131. In two patients abdominal lymphomas were incidentally found at the time of surgery for other diseases (hiatal hernia and cholelithiasis). There were no cases of documented malabsorption. Even though a majority of our patients had symptoms, 19 patients had normal preoperative examinations with no evidence of hepatosplenomegaly, palpable adenopathy, ascites, or abdominal mass (Table III). In five patients enlarged peripheral lymph nodes were noted shortly after surgery by other observers. No peripheral lymph nodes were biopsied before the initial surgery.

TABLE II

Presenting Symptoms

PrimarySite Stomach Patients (n) Pain Nausea, vomiting Weight loss Fatigue Diarrhea Constipation Sweats Fever None

TABLE III

9 7 3 4 4

SrIlall Bowel

Large Bowel 2 1

.. .

2

1 1

Mesentery

Retroperttoneum (Pancreas, Nodes)

Spleen

4 2 1 2 1

9 4 1 2 1

3 2 1 1 3

1

1 1 1

3 2

.

Physical Findlngs Primary Site Stomach

Patients (n) Abdominal mass Hepatomegaly Ascites Splenomegaly Peripheral lymphadenopathy’ Normal l

9 2 2

Small Bowel

Large Bowel

6 1

2

Mesenterv

Retroperitoneum (Pancreas, Nodes)

4 1

9 3

Spleen 3

.

3 1

.. ... . .

. . .

1

3

4

5

2

3

5

.

2 3

.

All noted by a second observer shortly after surgery.

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TABLE IV

Presurgical Radiologic Studies’ Primary Site Stomach

Small Bowel

Large Bowel

Mesentery

Retroperitoneum (Pancreas, Nodes)

Spleen

UGI

616

415

o/2

l/2

l/5

o/2

E Abdominal ultrasound IVP

0l/l l/2

214 0 O/l

212 0 0

l/2 l/l l/l

o/2 212 212

O/l l/l l/l

l/l

o/2

O/l

l/2

l/3

011

Number of abnormal studies/number performed. BE = barium enema; CT = computed tomography of the abdomen; IVP = intravenous pyelography; UGI = upper gastrointestinal series. l

TABLE V

ative notes. Only 18 patients (54 percent) had a liver biopsy. In 16 patients (48 percent) the spleen was not described. Only seven patients (21 percent) had splenectomy. There was no description of the size or appearance of regional lymph nodes in 7 patients (21 percent), and only 20 patients (60 percent) had regional lymph node biopsy. Only five patients (15 percent) had adequate surgical staging according to our criteria. Postsurgical staging (Table VII): No abdominal lymphangiography was done preoperatively. Bone scans and bone marrow biopsies were of little help. Only rarely did any of the postoperative studies yield results which were useful in directing therapy. Although we had no positive bone marrow biopsies in this review, many studies have demonstrated their importance in non-Hodgkin’s lymphomas [16]. Extent of disease and outcome (Table VIII): The overall survival rate for the group was 36 per-

Dlstributlon of Histologic Types n 4 2 23 1 1 1 1’

Poorly differentiated lymphocytic, diffuse Mixed lymphocytic-histiocytic, diffuse Histiocytic, diffuse Histiocytic, nodular “Lenrtert’s” lymphoma Undifferentiated tymphoma Hodgkin’s disease l

Originally diagnosed as histiocytic lymphoma.

managed as a non-Hodgkin’s lymphoma patient. A majority of our cases (69 percent) were diffuse histiocytic lymphoma, which is similar to the findings in other studies. Laparbtomy results (Table VI): In six patients (18 percent) the liver was not described in the oper-

TABLE VI

Results of Laparotomy Primary Site Stomach (n = 9)

Liver Not described “Looked normal” “Looked abnormal” Positive biopsy Negative biopsy Spleen Not described “Looked normal” “Looked abnormal” Positive biopsy Negative biopsy Nodes Not described “Looked normal” “Looked abnormal” Positive biopsy Negative biopsy

626

. . 3

. 2 4

Small Bowel (n = 6)

1 1

.. .. 4

1

4 2

... . .

. .. . 2

..

.. ..

3 4

2 2

2

Mesentery (n = 4)

Retroperitoneum (Pancreas, Nodes) (n = 9)

1 2

3 3

1

. . . .

5 1

3

Large Bowel fn = 2)

.

...

.

1

1 2

1 3

.

4 3 1

. ..

..

1

..

2

. . ... ..

Spleen In = 3)

. 1 2

. 3

. ..

2

.

.

3 1

1 1

1 1

.

1

...

...

4 1

2

..

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Surgical Staging in Abdominal

cent, which is similar to that reported in other series of gastrointestinal lymphoma [12,13]. It is impossible to evaluate individual modes of therapy because of the different approaches used. Comments Recent studies have shown that patients with abdominal lymphomas have a poor prognosis even with aggressive chemotherapy and radiotherapy [12,13]. Prognostic factors recognized in past studies include regional node involvement, dissemination of disease beyond the regional nodes, and tumor size, but no randomized prospective studies evaluating therapy have been done [ll ,I 71. Before rational treatment can be planned there must be accurate staging of the disease. The definition of the extent of disease as well as any systemic spread is important in determining radiotherapy ports and the need for chemotherapy. The purpose of our study was to determine the adequacy of surgical staging in patients with primary abdominal lymphoma seen at a referral center. Our data show that surgical staging is often inadequate. Only 54 percent of our patients had a liver biopsy, and only 60 percent had sampling of regional nodes. In 48 percent there was no description of the spleen, and splenectomy was performed in only 21 percent. Based on our definition of adequate surgical staging, only 15 percent of patients were adequately staged. This is similar to the findings reported by Heifetz et al [18]. Unfortunately, postoperative radiographic and nucleotide studies add little useful staging information. Unlike lymphoma presenting in other sites, most patients with abdominal lymphoma are operated on with no previous suspicion of the diagnosis. The surgery is usually done by general surgeons, who unfortunately do little systematic surgical staging. The patients who have undergone laparotomy recently are rarely subjected to a second staging laparotomy even though the initial staging procedures were inadequate. Thus the initial surgical procedure is crucial for gathering data for subsequent therapeutic decisions. In our series five patients were noted to have peripheral adenopathy by a second observer. If a lymph

TABLE VIII

TABLE VII

Lymphoma

Results of Postsurglcal Staging Procedures

Study

(n)

Abnormal Study

Normal Study

Bipedal lymphangiogram Liver-spleen scan Bone scan Bone marrow biopsy

17 17 13 22

8 6 2 0

9 11 11 22

Patients

node biopsy can be obtained before laparotomy, thus establishing the diagnosis, the staging laparotomy can be approached in an organized and systematic manner. Occasionally, adequate surgical staging cannot be done because of the patient’s condition or because the diagnosis is not apparent at surgery. However, if the diagnosis is made or considered at the time of laparotomy, the following are recommended: the primary site of disease should be determined, the size of the tumor and any extension to other organs should be described, and, if possible, the tumor should be resected. Several investigators suggest that complete resection improves survival even in the face of disseminated disease [12,17]. This may decrease the incidence of perforation and gastrointestinal bleeding, which are major causes of morbidity and mortality in these patients [ 121. If complete resection is not possible, then the tumor mass should be marked with metal clips. This gives important information to the radiotherapist in defining radiotherapy ports. Regional lymph nodes and any abnormal-appearing lymph nodes should be biopsied. Even if not clinically involved, biopsies of iliac, mesenteric, and paraaortic nodes should be performed. The liver should be examined and biopsied even if it appears normal on inspection. The gross appearance and size of the spleen should be described and, if technically possible, splenectomy should be performed. A bone marrow biopsy should be done. A careful examination and description of the remainder of the abdomen is indicated because multiple intestinal lesions are frequently encountered (in 10 to 21 percent of cases) [I I].

Extent of Disease and OutCOme

Patients Stage

(n)

I

6 7 3 11 6

IE

II llE

IV

Results of Therapy PR CR 3 5 1 6 3

3 2 2 5 3

n 2 2 1 4 3

Outcome Disease-Free Months 17+, 34-k, 86+ 15+, 21+,

32+ 41+ 2a+, 30+, 44-f 30+, 38+

Death 4 5’ 2 7 3

Two patients died while in complete remission, one from infection and one from adenocarcinoma of the lung. CR = complete remission; PR = partial remission. l

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Summary At present there is no consensus on the optimal management of patients with abdominal lymphomas. One major obstacle in treatment planning is the lack of adequate surgical staging. A retrospective review of 33 consecutive patients presenting with abdominal lymphoma revealed that the initial surgical procedures were deficient in most cases. Frequent omissions were failure to biopsy the regional lymph nodes and liver, lack of splenectomy, and lack of adequate description of the spleen. Until prospective studies of various treatment regimens can be carried out in adequately surgically staged patients with abdominal lymphomas, no clear treatment recommendations can be made. Surgical staging should include description, biopsy, and (if possible) resection of the primary tumor; description and biopsy of involved and regional lymph nodes; biopsy of the liver; description of and (if possible) resection of the spleen; and bone marrow biopsy.

13.

References

14.

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