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Pseudolymphoma of the Stomach
Symposium on Unexpected Presentations of Surgical Disease
Pseudolymphoma of the Stomach Ransom R. Buchholz, MD., and Raymond A. Reid, MD.
The importance of the recognition of a benign lesion of the stomach which may mimic gastric carcinoma or gastric lymphosarcoma is obvious. Though gastric carcinoma continues to be associated with a poor prognosis, a generally good prognosis has been exhibited in reported cases of gastric lymphosarcoma. 2 , 5, 12 In 1958, after a study of 131 cases of lymphosarcoma of the stomach, Smith and Helwig 15 reported that 42 were, in reality, lymphoproliferative disorders which had been termed pseudolymphoma. They indicated from their findings that the inclusion of some cases of this benign disorder in reported series of gastric malignant lymphoma has been the explanation for the high survival rates for gastric lymphoma. Others have also presented evidence to support this view. 3 • 6 The clinical, radiological, and pathological findings in 15 cases of pseudolymphoma of the stomach were described by Perez and Dorfman 1:3 in 1966. Pseudolymphomas fulfilling essentially the same histopathologic criteria have also been reported in other areas, including lung, 10, 14 anterior mediastinum,4 skin," lacrimal gland/ parotid,8 and soft tissue. 1
CASE REPORT
J,
A 71 year old man was admitted with a 5 year history of vague upper abdominal complaints, In 1967 this patient had an episode of persistent nausea and vomiting of 6 days' duration, with hematemesis on one occasion, Results of an upper gastrointestinal series, barium enema, and gallbladder series were reported to be negative, He was readmitted in 1969 with a recurrence of epigastric pain of several weeks duration, nausea, and vomiting. A gastrointestinal series revealed evidence of large rugae in the antrum with some narrowing in this area, There was a large diverticulum of the duodenum, He improved on diet and antacids, The patient was again admitted on January 20, 1970 with a history of abdominal pain, nausea, and vomiting, of four months' duration, and a weight loss of 30 pounds, The hemoglobin was 15 gm,; SMA was within From the Departments of Surgery and Pathology, Veterans Administration Center, Temple, Texas
Surgical Clinics of North America- Vol. 52, No.2, April 1972
485
486
RANSOM
R.
BUCHHOLZ AND RAYMOND
A.
REID
normal limits. Gastric analysis revealed no free acid. Stools were negative for occult blood. A gastrointestinal series revealed a normal esophagus. A defect (Fig. 1) with a crater was seen along the greater curvature just above the level of the incisura. Prominent rugae were present. On J anurary 28 a gastroscopic examination was performed with a fiberoptic gastroscope: "Just as seen on x-ray, proximal to the angulus, there is a 2 x 3 cm., irregular, necrotic ulceration which is surrounded by numerous reddish-grey nodules. This nodularity extends 7 to 8 cm. up the greater curvature and posterior wall. The gastric wall was rigid. Photographs were taken." A gastroscopic diagnosis of carcinoma of the stomach was made. On February 2, at the time of abdominal exploration, an intragastric mass with crater formation was palpated on the greater curvature, extending on the posterior wall of the stomach at the angulus. The ulcer did not extend to the serosa. Only a few small soft lymph nodes were present in the mesocolon. The liver was smooth and grossly free of metastases. The surgeon thought the lesion was a large gastric ulcer or a carcinoma. A 75 per cent gastric resection was performed with concomitant excision of the greater omentum. The spleen was not included in the resection. Continuity of the gastrointestinal tract was re-established by Hofmeister modification of the Billroth II principle. The patient's postoperative course was uneventful, and he was discharged from the hospital on the twelfth postoperative day. Eighteen months after surgery, an upper gastrointestinal series revealed a normal postgastrectomy pouch with no defects. The patient had no gastrointestinal complaints.
Figure 1. Defect and crater visualized along greater curvature.
PSEUDOL YMPHOMA OF THE STOMACH
487
PATHOLOGY The gross specimen consisted of a segment of the distal stomach (Fig. 2). There was a penetrating ulcer of the posterior wall of the organ which measured 3.0 x 1. 7 cm. The base of the ulcer was indurated and the musculature of the stomach wall overlying the base of the crater was mildly thickened. The edges of the ulcer crater were well demarcated, with slightly hyperplastic overhanging mucosal margins. Microscopically, there was loss of continuity of the mucosal lining at the site of the ulcer which penetrated through the lamina propria into the submucosa. There was a band of lymphoid tissue (Fig. 3) involving the lamina propria and the outer portion of the submucosa, in which well defined lymphoid follicles with active germinal centers were a prominent feature. The lesion was sharply delineated at its base and the underlying submucosa was edematous. There were minimal foci of chronic inflammatory infiltrate in the muscle coat. The predominant cell type was the mature lymphocyte (Fig. 4), with a scattering of plasma cells and histiocytes. Eosinophils were rare and polymorphonuclear leukocytes were seen in insignificant numbers. Within the lymphoid follicles, the germinal centers were active and occasional mitotic figures were noted (Fig. 5). The absence of mitotic figures in the diffuse infiltrate outside the germinal centers, together with the finding of relatively small lymphoid follicles without coalescence, was evidence against a malignant lymphoma. Absence of abnormal histiocytes, multinucleated giant cells of the Reed Sternberg Type, fibrosis, and necrosis also represent evidence of the benign nature of the process. Several lymph nodes from the omentum in the vicinity of the ulcer exhibited only chronic inflammation and mild reticulum cell hyperplasia, with no evidence of lymphomatous involvement.
DISCUSSION Gastric pseudolymphoma was established as a clinical entity by descriptions of the entity by Smith and Helwig 15 and Jacobs. 9 Watson and O'Brien 16 tabulate an excellent differentiation between the malignant lymphoma and pseudolymphoma (Table 1). Histological examination is at present the main procedure available to differentiate lymphosarcoma from pseudolymphoma. From a radiological viewpoint, the diagnosis is difficult because pseudolymphoma may simulate any type of malignant tumor and also benign gastric ulcer. Perez and Dorfman 1;] state that 50 per cent of the cases in their series were interpreted as polypoid, infiltrating, or ulcerating carcinoma. Obvious ulceration was present in two-thirds of their cases. Clinically, these patients relate a rather long period of gastric complaints, usually without a palpable abdominal mass. Our patient reported at least a 5 year history suggestive of peptic ulcer disease. Most of the reported cases were over 40 years of age, with the average being 57 years. Since gastric resection is an accepted procedure for both gastric ulcer and gastric lymphoma, it would seem that gastric resection would be the
488
RANSOM
Figure 2.
R.
BUCHHOLZ AND RAYMOND
A.
REID
Photograph of resected stomach showing ulcer.
Figure 3. Lesion as viewed by scanning lens exhibits a wide band of lymphoid tissue, sharply delineated at its base, which is virtually obliterating the lamina propria and outer portion of the submucosa. Small lymphoid follicles, with reactive germinal centers, exhibit no tendency to coalesce. The ulcer is not shown on the photomicrograph. (x 35).
489
PSEUDOL YMPHOMA OF THE STOMACH
Figure 4. High magnification view shows lamina propria involved by a dense mixed inflammatory infiltrate. The predominant cell type is the mature lymphocyte, but occasional plasma cells, histiocytes and eosinophiles are noted. 400)
ex
Figure 5. Photomicrograph at high magnification reveals mitotic figures present only within the reactive germinal center (lower left) of a lymphoid follicle. 400)
ex
490
RANSOM
Table 1.
R. BUCHHOLZ AND RAYMOND A. REID
Histologic Features of Pseudolymphoma and Lymphocytic Lymphoma of the Stomach
PSEUDOLYMPHOMA
LYMPHOCYTIC LYMPHOMA
Essential diagnostic features
Essential diagnostic features
Follicle formation with true germinal centers Lymphocytic cell type Absence of lymph node involvement
Contributory features
Contributory features Nodular arrangement to architecture Mixed inflammatory infiltration Mitotic figures confined to reaction centers Over·all increase of scar tissue and reactive changes Supportive features Sharp clear-cut borders present Usually overhanging margins Ulceration of mucosa almost always present
Lack of follicle formation with true germinal centers Anaplasia and pleomorphism of cells Involvement of regional lymph nodes
Sheets of pure lymphocytes vs. a mixed infiltrate Mural invasion that extends through the serosal surface
Supportive features Widespread reticulum which surrounds and separates small groups of cells Vascular invasion Tends to multiplicity of mucosal ulcers
procedure of choice in this entity. Ulceration is a frequent gross pathological finding.
SUMMARY A case of pseudolymphoma of the stomach is presented. The clinical, radiographic, gastroscopic, and pathological findings are described. The histopathological features are consistent with pseudolymphoma. The essential diagnostic features of follicle formation, with true germinal centers, lymphocytic cell type, and absence of lymph node involvement, as elaborated by Smith and Helwig,15 are present. Several contributory and supportive features, as stated in the criteria of these authors, are also met, including nodular arrangement of architecture and mitotic figures confined to the reactive germinal centers. Similar lesions of the stomach, often associated with ulcerations, are reported by Jacobs 9 and others. The inclusion of patients with pseudolymphomas, a benign lesion that may be confused with lymphosarcoma, may be the explanation for the variation in the clinical course in reported series of patients with gastric lymphosarcoma. Pseudolymphoma of the stomach may be a variation of chronic gastric ulcer.
PSEUDOLYMPHOMA OF THE STOMACH
491
REFERENCES 1. Ackerman, L. V., and del Regato, J. A.: Cancer: Diagnosis, Treatment, and Prognosis. St. Louis, Missouri, C. V. Mosby, 3rd ed., 1962. 2. Allen, A. W., Donaldson, G., Sniffen, R C., and Goodale, F., Jr.: Primary malignant lymphoma of gastrointestinal tract. Ann. Surg., 140:428-438 (Sept.) 1954. 3. Berry, G. R, and Mathews, W. H.: Gastric lymphosarcoma and pseudolymphoma: Reappraisal of 12 cases of gastric lymphosarcoma. Canad. Med. Assoc. J., 96:1312-1316 (May) 1967. 4. Castleman, B., Iverson, L., and Pardo Menendez, V.: Localized mediastinal lymph node hyperplasia resembling thymoma. Cancer, 9:822-830 (July-Aug.) 1956. 5. Ellis, H. A., and Lannigan, R: Primary lymphoid neoplasms of the stomach. Gut, 4:145-152 (June) 1963. 6. Faris, T. D., and Saltzstein, S. L.: Gastric lymphoid hyperplasia: A lesion confused with lymphosarcoma. Cancer 17:207-212 (Feb.) 1964. 7. Font, R L., Yanoff, M., and Zimmerman, L. E.: Benign lymphoepithelial lesion of the lacrimal gland and its relationship to Sjogren's syndrome. Amer. J. Clin. Path., 48:365-376 (Oct.) 1967. 8. Godwin, J. T.: Benign lymphoepitheliallesion of the parotid gland: Report of 11 cases. Cancer, 5:1089-1103 (Nov.) 1952. 9. Jacobs, D. S.: Primary gastric malignant lymphoma and pseudolymphoma. Amer. J. Clin. Path., 40:379-394 (Oct,) 1963. 10. Lattes, R, and Pachter, M. R: Benign lymphoid masses of probable harmartomatous nature: Analysis of 12 cases. Cancer, 15:197-214 (Jan.-Feb.) 1962. 11. Mopper, C., and Rogin, J. R: Benign solitary lymphocytoma: Report of 3 cases. Arch. Derm. Syph., 63:184-190 (Feb.) 1951. 12. McN$!er, G., and Berg, J. W.: The clinical behavior and management of primary malignant lymphoma of the stomach. Surg., 46:829-840 (Nov.) 1959. 13. Perez, C. A., and Dorfman, R F.: Benign lymphoid hyperplasia of the stomach and duodenum. Radiology, 87:505-510 (Sept.) 1966. 14. Saltzstein, S. L.: Pulmonary malignant lymphomas and pseudolymphomas: Classification, therapy, and prognosis. Cancer, 16:928-955 (July) 1963. 15. Smith, J. L., Jr., and Helwig, E. B.: Malignantlymphoma of the stomach: Its diagnosis, distinction and biologic behavior. Amer. J. Path., 34:553 (May-june) 1958. 16. Watson, R J., and O'Brien, M. T.: Gastric pseudolymphoma (lymphofollicular gastritis). Ann. Surg., 171 :98-106 (Jan.) 1970. Veterans Administration Center Temple, Texas 76501
Pseudolymphoma of the Stomach Ransom R. Buchholz, MD., and Raymond A. Reid, MD.
The importance of the recognition of a benign lesion of the stomach which may mimic gastric carcinoma or gastric lymphosarcoma is obvious. Though gastric carcinoma continues to be associated with a poor prognosis, a generally good prognosis has been exhibited in reported cases of gastric lymphosarcoma. 2 , 5, 12 In 1958, after a study of 131 cases of lymphosarcoma of the stomach, Smith and Helwig 15 reported that 42 were, in reality, lymphoproliferative disorders which had been termed pseudolymphoma. They indicated from their findings that the inclusion of some cases of this benign disorder in reported series of gastric malignant lymphoma has been the explanation for the high survival rates for gastric lymphoma. Others have also presented evidence to support this view. 3 • 6 The clinical, radiological, and pathological findings in 15 cases of pseudolymphoma of the stomach were described by Perez and Dorfman 1:3 in 1966. Pseudolymphomas fulfilling essentially the same histopathologic criteria have also been reported in other areas, including lung, 10, 14 anterior mediastinum,4 skin," lacrimal gland/ parotid,8 and soft tissue. 1
CASE REPORT
J,
A 71 year old man was admitted with a 5 year history of vague upper abdominal complaints, In 1967 this patient had an episode of persistent nausea and vomiting of 6 days' duration, with hematemesis on one occasion, Results of an upper gastrointestinal series, barium enema, and gallbladder series were reported to be negative, He was readmitted in 1969 with a recurrence of epigastric pain of several weeks duration, nausea, and vomiting. A gastrointestinal series revealed evidence of large rugae in the antrum with some narrowing in this area, There was a large diverticulum of the duodenum, He improved on diet and antacids, The patient was again admitted on January 20, 1970 with a history of abdominal pain, nausea, and vomiting, of four months' duration, and a weight loss of 30 pounds, The hemoglobin was 15 gm,; SMA was within From the Departments of Surgery and Pathology, Veterans Administration Center, Temple, Texas
Surgical Clinics of North America- Vol. 52, No.2, April 1972
485
486
RANSOM
R.
BUCHHOLZ AND RAYMOND
A.
REID
normal limits. Gastric analysis revealed no free acid. Stools were negative for occult blood. A gastrointestinal series revealed a normal esophagus. A defect (Fig. 1) with a crater was seen along the greater curvature just above the level of the incisura. Prominent rugae were present. On J anurary 28 a gastroscopic examination was performed with a fiberoptic gastroscope: "Just as seen on x-ray, proximal to the angulus, there is a 2 x 3 cm., irregular, necrotic ulceration which is surrounded by numerous reddish-grey nodules. This nodularity extends 7 to 8 cm. up the greater curvature and posterior wall. The gastric wall was rigid. Photographs were taken." A gastroscopic diagnosis of carcinoma of the stomach was made. On February 2, at the time of abdominal exploration, an intragastric mass with crater formation was palpated on the greater curvature, extending on the posterior wall of the stomach at the angulus. The ulcer did not extend to the serosa. Only a few small soft lymph nodes were present in the mesocolon. The liver was smooth and grossly free of metastases. The surgeon thought the lesion was a large gastric ulcer or a carcinoma. A 75 per cent gastric resection was performed with concomitant excision of the greater omentum. The spleen was not included in the resection. Continuity of the gastrointestinal tract was re-established by Hofmeister modification of the Billroth II principle. The patient's postoperative course was uneventful, and he was discharged from the hospital on the twelfth postoperative day. Eighteen months after surgery, an upper gastrointestinal series revealed a normal postgastrectomy pouch with no defects. The patient had no gastrointestinal complaints.
Figure 1. Defect and crater visualized along greater curvature.
PSEUDOL YMPHOMA OF THE STOMACH
487
PATHOLOGY The gross specimen consisted of a segment of the distal stomach (Fig. 2). There was a penetrating ulcer of the posterior wall of the organ which measured 3.0 x 1. 7 cm. The base of the ulcer was indurated and the musculature of the stomach wall overlying the base of the crater was mildly thickened. The edges of the ulcer crater were well demarcated, with slightly hyperplastic overhanging mucosal margins. Microscopically, there was loss of continuity of the mucosal lining at the site of the ulcer which penetrated through the lamina propria into the submucosa. There was a band of lymphoid tissue (Fig. 3) involving the lamina propria and the outer portion of the submucosa, in which well defined lymphoid follicles with active germinal centers were a prominent feature. The lesion was sharply delineated at its base and the underlying submucosa was edematous. There were minimal foci of chronic inflammatory infiltrate in the muscle coat. The predominant cell type was the mature lymphocyte (Fig. 4), with a scattering of plasma cells and histiocytes. Eosinophils were rare and polymorphonuclear leukocytes were seen in insignificant numbers. Within the lymphoid follicles, the germinal centers were active and occasional mitotic figures were noted (Fig. 5). The absence of mitotic figures in the diffuse infiltrate outside the germinal centers, together with the finding of relatively small lymphoid follicles without coalescence, was evidence against a malignant lymphoma. Absence of abnormal histiocytes, multinucleated giant cells of the Reed Sternberg Type, fibrosis, and necrosis also represent evidence of the benign nature of the process. Several lymph nodes from the omentum in the vicinity of the ulcer exhibited only chronic inflammation and mild reticulum cell hyperplasia, with no evidence of lymphomatous involvement.
DISCUSSION Gastric pseudolymphoma was established as a clinical entity by descriptions of the entity by Smith and Helwig 15 and Jacobs. 9 Watson and O'Brien 16 tabulate an excellent differentiation between the malignant lymphoma and pseudolymphoma (Table 1). Histological examination is at present the main procedure available to differentiate lymphosarcoma from pseudolymphoma. From a radiological viewpoint, the diagnosis is difficult because pseudolymphoma may simulate any type of malignant tumor and also benign gastric ulcer. Perez and Dorfman 1;] state that 50 per cent of the cases in their series were interpreted as polypoid, infiltrating, or ulcerating carcinoma. Obvious ulceration was present in two-thirds of their cases. Clinically, these patients relate a rather long period of gastric complaints, usually without a palpable abdominal mass. Our patient reported at least a 5 year history suggestive of peptic ulcer disease. Most of the reported cases were over 40 years of age, with the average being 57 years. Since gastric resection is an accepted procedure for both gastric ulcer and gastric lymphoma, it would seem that gastric resection would be the
488
RANSOM
Figure 2.
R.
BUCHHOLZ AND RAYMOND
A.
REID
Photograph of resected stomach showing ulcer.
Figure 3. Lesion as viewed by scanning lens exhibits a wide band of lymphoid tissue, sharply delineated at its base, which is virtually obliterating the lamina propria and outer portion of the submucosa. Small lymphoid follicles, with reactive germinal centers, exhibit no tendency to coalesce. The ulcer is not shown on the photomicrograph. (x 35).
489
PSEUDOL YMPHOMA OF THE STOMACH
Figure 4. High magnification view shows lamina propria involved by a dense mixed inflammatory infiltrate. The predominant cell type is the mature lymphocyte, but occasional plasma cells, histiocytes and eosinophiles are noted. 400)
ex
Figure 5. Photomicrograph at high magnification reveals mitotic figures present only within the reactive germinal center (lower left) of a lymphoid follicle. 400)
ex
490
RANSOM
Table 1.
R. BUCHHOLZ AND RAYMOND A. REID
Histologic Features of Pseudolymphoma and Lymphocytic Lymphoma of the Stomach
PSEUDOLYMPHOMA
LYMPHOCYTIC LYMPHOMA
Essential diagnostic features
Essential diagnostic features
Follicle formation with true germinal centers Lymphocytic cell type Absence of lymph node involvement
Contributory features
Contributory features Nodular arrangement to architecture Mixed inflammatory infiltration Mitotic figures confined to reaction centers Over·all increase of scar tissue and reactive changes Supportive features Sharp clear-cut borders present Usually overhanging margins Ulceration of mucosa almost always present
Lack of follicle formation with true germinal centers Anaplasia and pleomorphism of cells Involvement of regional lymph nodes
Sheets of pure lymphocytes vs. a mixed infiltrate Mural invasion that extends through the serosal surface
Supportive features Widespread reticulum which surrounds and separates small groups of cells Vascular invasion Tends to multiplicity of mucosal ulcers
procedure of choice in this entity. Ulceration is a frequent gross pathological finding.
SUMMARY A case of pseudolymphoma of the stomach is presented. The clinical, radiographic, gastroscopic, and pathological findings are described. The histopathological features are consistent with pseudolymphoma. The essential diagnostic features of follicle formation, with true germinal centers, lymphocytic cell type, and absence of lymph node involvement, as elaborated by Smith and Helwig,15 are present. Several contributory and supportive features, as stated in the criteria of these authors, are also met, including nodular arrangement of architecture and mitotic figures confined to the reactive germinal centers. Similar lesions of the stomach, often associated with ulcerations, are reported by Jacobs 9 and others. The inclusion of patients with pseudolymphomas, a benign lesion that may be confused with lymphosarcoma, may be the explanation for the variation in the clinical course in reported series of patients with gastric lymphosarcoma. Pseudolymphoma of the stomach may be a variation of chronic gastric ulcer.
PSEUDOLYMPHOMA OF THE STOMACH
491
REFERENCES 1. Ackerman, L. V., and del Regato, J. A.: Cancer: Diagnosis, Treatment, and Prognosis. St. Louis, Missouri, C. V. Mosby, 3rd ed., 1962. 2. Allen, A. W., Donaldson, G., Sniffen, R C., and Goodale, F., Jr.: Primary malignant lymphoma of gastrointestinal tract. Ann. Surg., 140:428-438 (Sept.) 1954. 3. Berry, G. R, and Mathews, W. H.: Gastric lymphosarcoma and pseudolymphoma: Reappraisal of 12 cases of gastric lymphosarcoma. Canad. Med. Assoc. J., 96:1312-1316 (May) 1967. 4. Castleman, B., Iverson, L., and Pardo Menendez, V.: Localized mediastinal lymph node hyperplasia resembling thymoma. Cancer, 9:822-830 (July-Aug.) 1956. 5. Ellis, H. A., and Lannigan, R: Primary lymphoid neoplasms of the stomach. Gut, 4:145-152 (June) 1963. 6. Faris, T. D., and Saltzstein, S. L.: Gastric lymphoid hyperplasia: A lesion confused with lymphosarcoma. Cancer 17:207-212 (Feb.) 1964. 7. Font, R L., Yanoff, M., and Zimmerman, L. E.: Benign lymphoepithelial lesion of the lacrimal gland and its relationship to Sjogren's syndrome. Amer. J. Clin. Path., 48:365-376 (Oct.) 1967. 8. Godwin, J. T.: Benign lymphoepitheliallesion of the parotid gland: Report of 11 cases. Cancer, 5:1089-1103 (Nov.) 1952. 9. Jacobs, D. S.: Primary gastric malignant lymphoma and pseudolymphoma. Amer. J. Clin. Path., 40:379-394 (Oct,) 1963. 10. Lattes, R, and Pachter, M. R: Benign lymphoid masses of probable harmartomatous nature: Analysis of 12 cases. Cancer, 15:197-214 (Jan.-Feb.) 1962. 11. Mopper, C., and Rogin, J. R: Benign solitary lymphocytoma: Report of 3 cases. Arch. Derm. Syph., 63:184-190 (Feb.) 1951. 12. McN$!er, G., and Berg, J. W.: The clinical behavior and management of primary malignant lymphoma of the stomach. Surg., 46:829-840 (Nov.) 1959. 13. Perez, C. A., and Dorfman, R F.: Benign lymphoid hyperplasia of the stomach and duodenum. Radiology, 87:505-510 (Sept.) 1966. 14. Saltzstein, S. L.: Pulmonary malignant lymphomas and pseudolymphomas: Classification, therapy, and prognosis. Cancer, 16:928-955 (July) 1963. 15. Smith, J. L., Jr., and Helwig, E. B.: Malignantlymphoma of the stomach: Its diagnosis, distinction and biologic behavior. Amer. J. Path., 34:553 (May-june) 1958. 16. Watson, R J., and O'Brien, M. T.: Gastric pseudolymphoma (lymphofollicular gastritis). Ann. Surg., 171 :98-106 (Jan.) 1970. Veterans Administration Center Temple, Texas 76501