Malignant Lymphoma #

In a historical review of malignant lymphoid tumors of the gastrointestinal tract, Dawson et al (l96l) found that these tumors had been reported more frequently in the stomach than in the remainder of the digestive tract. Up to that time at least 293 reports of lymphoid tumors of the stomach had appeared in the literature, but no clear distinction had been made between lymphomas originating primarily in the stomach and those affecting the stomach as a manifestation of generalized, disseminated lymphomatous disease. According to these authors the tumors could be classified as primary if the following conditions were met: there should be no palpable superficial lymphadenopathy and no enlargement of the mediastinal lymph nodes; the total and differential white blood count should be within normal limits; at laparotomy the bowel (or gastric) lesion should predominate, the only lymph nodes obviously affected being those in its immediate neighbourhood; and finally the liver and spleen should be free of tumor.

Rappaport (l966) proposed a histological classification of the lymphomas which also included Hodgkin's disease. For the past two or three decades his classification, as well as five or six others, have been widely used.

Naqvi et al. (l969) found that approximately 1,200 cases of gastric lymphomas had been recorded, and reviewed 100 cases of their own. In their experience the stomach was the part of the gastrointestinal tract most frequently involved, and the prepyloric region the site most commonly affected.

In discussing the pathology Ming (l973) stated that, in the stomach, malignant lymphoma develops in the mucosa, from where the tumor cells infiltrate the submucosa and muscularis. Seeing that this mode of growth is similar to that of carcinoma, it often assumes the gross characteristics of carcinoma and macroscopic differentiation of the two conditions may be difficult. Grossly the tumors may be ulcerated with rolled borders, while others are polypoid. There may be extensive infiltration and thickening of the gastric wall and/or mucosal folds. Histologically there is dense infiltration, with varying degrees of admixture of mature and immature lymphoid cells and histiocytic (reticulum) cells; there is a lack of fibrous tissue proliferation. While mucosal glands may be absent, the remaining gastric glands usually retain their normal architecture. The presence of reticulum fibres and absence of stainable mucin are features in favour of lymphoma (as opposed to carcinoma).

Katz et al. (l973) described 15 cases of disseminated lymphoma with gastric involvement. The following abnormal findings were noted at gastroscopy: enlarged, nondistensible rugae in 13 cases, multiple superficial ulcerations in 11, nodular ulcerations in 8 and large polypoid masses in 4. Biopsy furnished a positive diagnosis in not more than 2 of the 15 cases. The poor yield was ascribed to the infiltrative submucosal nature of secondary lymphoma and the superficial capacity of endoscopic biopsies. The gastroscopic appearance was found to be of greater help in the diagnosis of gastric lymphoma than biopsies, directed brush cytology or cytology washings.

Meyers et al. (l975) pointed out that the radiographic features of primary gastric lymphoma were not specific and included polypoid masses, ulcerations, thickening of the walls and generalized enlargement of the rugae. These appearances could simulate ulcerated carcinoma, gastric ulceration, granulomatous disease or hypertrophic rugae due to other causes, e.g. Menetrier's disease. While lymphoma may occur anywhere in the stomach, they reiterated that it commonly involved the pyloric and prepyloric area. In 7 proved cases they noted a definite tendency for the condition to spread submucosally from the distal stomach into the duodenum, resulting in radiographically discernible contour deformities, filling defects or ulcerations in the duodenal bulb. These features seldom occur in gastric adenocarcinoma (Chap. 33), and were regarded as characteristic of lymphoma, permitting a specific diagnosis to be made. In one of their cases, which was described in detail, duodenal spread occurred both superficial and deep to the lamina propria. This surrounded, but apparently did not invade, the glands of Brunner.

Koehler et al. (l977) analyzed the records of l9 patients who underwent gastric resection for lymphoma. Three of these had microscopic evidence of invasion of the duodenum, and in one of these the duodenal involvement was evident radiographically and grossly.

Lim et al. (l977) defined primary gastric lymphoma as a tumor apparently originating in the stomach, with no clinical, laboratory or radiographic evidence of systemic involvement at the time of initial evaluation. They analyzed 50 consecutive cases and found the most common localities to be the "antrum", the pyloric area and lesser curvature. According to Rappaport's (1966) classification, the diffuse histiocytic type occurred in 23 of their 50 patients, the well differentiated lymphocytic type in 12, the mixed lymphocytic histiocytic in 5, the poorly differentiated lymphocytic in 5, Hodgkin's disease in 3, and unclassified lymphoma in 2 cases. The prognosis for survival was much better than in gastric carcinoma since the latter condition presented with a far higher incidence of serosal penetration and nodal and distant metastases. The treatment of choice was gastric resection (44 of their cases being resectable), while radiotherapy and chemotherapy constituted additional therapeutic options.

Seeing that the therapy and prognosis of gastric lymphoma differ significantly from those of adenocarcinoma, Hricak et al. (l980) reiterated that correct diagnosis was essential. By reviewing the radiographic and pathological features in 81 cases, they investigated the incidence of spread from the stomach into the oesophagus, and from the stomach into the duodenum. In 60 of the cases the tumor appeared to have originated primarily in the stomach, and only 5 of these showed involvement of adjacent nodes, the mesentery or small bowel. In 21 patients the involvement was mainly extrinsic, the stomach being secondarily involved. Radiographically transpyloric extension was seen in 27 of the 81 cases. In 7 the "antrum" was the only site of tumor involvement, 6 of these showing transpyloric extension. Histologically the tumor was found to have a submucosal origin (according to Ming it originated in the mucosa). Submucosal extension across the pylorus was seen in l9 of the 27 cases. Zornoza and Dodd (l980) pointed out that the gross appearance and microscopic characteristics of the lesion were identical in the primary gastric and disseminated forms. The only differences between them were the distribution of the disease and the potential for future spread. Disseminated lymphoma was a lethal process that ran a rapid course. Although moderate stiffening of the gastric walls might occur in the intraluminal fungating form, peristaltic waves were not completely absent. The diffusely enlarged and distorted gastric rugae appeared to be more or less fixed.

Craig and Gregson (l98l) reiterated that one of the findings strongly suggesting the diagnosis of lymphoma was mucosal involvement extending across the pylorus into the duodenum. The US National Cancer Institute (l982), in a retrospective study of over 1,000 cases, published a revised and modified classification of non-Hodgkin's lymphoma based on six previous classifications, including that of Rappaport (l966). This has become known as the "Working Formulation for non-Hodgkin's Lymphomas". It is based primarily on clinical correlations, especially survival curves, age, sex, presenting sites and stage of the disease. Other recent classifications have been based, in part, upon modern concepts of the immune system and lymphoid physiology.

According to Sandler (l984), whose views differ from those of Ming (l973), primary gastric lymphomas arise from lymphoid tissue in the lamina propria and extend laterally along the submucosal layer. As the mucosa is not involved in the first place, endoscopy and endoscopic biopsy are unreliable diagnostic modalities. The muscular layer is generally spared till a late stage of the disease. The diffuse infiltration by mature and immature lymphoid cells and histiocytic cells may result in large, rigid folds or the appearance of linitis plastica. The lesions may also be of a polypoid or fungating nature. They do not constrict the lumen or interfere with peristalsis, and pyloric obstruction is unusual.

Because the tumor is predominantly submucosal, the diagnosis of gastric lymphoma by endoscopic biopsy can be difficult, according to Fork et al. (l985); in one report a success rate of only 44 percent was achieved.

Only a few cases of malignant gastric lymphomatous disease have been encountered in our department in many thousands of upper gastrointestinal barium investigations during the past 3 to 4 years. The following are two of the cases:

Case Reports #

Case 34.1 G.C., l7 year old male, had a two year history of epigastric pain, vomiting, weight loss and retardation of growth. Physical examination revealed severe iron deficiency anaemia. Radiographic study showed multiple lobulated filling defects in the corpus and sinus of the stomach, constant irregularity of the greater and lesser curvatures and a narrowing at the commencement of the pyloric sphincteric cylinder, in the region of the left pyloric loop (Fig. 34.1). The cylinder was partially contracted throughout the examination, never contracting or relaxing maximally; this was associated with a patent pyloric aperture measuring 4.0 mm in diameter. Gastric emptying of fluid barium was delayed. Endoscopy showed diffuse, nodular infiltration of the entire corpus and "antrum", with contact bleeding. The infiltration surrounded the pyloric orifice, which was patent. The duodenum could not be visualized. Histology, according to the "Working Formulation", revealed a high grade, malignant, non-Hodgkin lymphoma. Bone marrow biopsy was normal.

Fig. 34.1. Case G.C. Irregularities of lesser and greater curvatures extending to commencement of pyloric sphincteric cylinder. Cylinder partially contracted (arrows). Pyloric aperture patent

At operation the entire stomach from the gastro-oesophageal junction to the pylorus was found to be involved by lymphomatous infiltration, and a total gastrectomy with an oesophago-jejunal anastomosis was performed. Macroscopically the resection specimen showed diffuse thickening of the walls with effacement of the normal mucosal pattern. Microscopically tumor cells extended from the mucosa into the muscular layer and in several areas as far as the serosa. Electron microscopically the cells were determined to belong to the lymphoma group, the condition being diagnosed by a combination of light microscopy, electron microscopy and immunocytology as a large cell (B-cell), immunoblastic lymphoma. The distal border of the resection specimen was free of tumor cells and liver biopsy was normal. A few enlarged mesenteric lymph nodes proved to be of reactive type.

Case 34.2 J.J., 43 year old male, presented with intermittent epigastric pain, vomiting, loss of appetite and loss of weight, of one year's duration. Physical examination revealed epigastric tenderness. Radiographic study showed a constant irregularity of the lower part of the lesser curvature, with a permanent, ulcer-like projection; a large, lobulated filling defect was present in the duodenal bulb (Fig. 34.2). The pyloric sphincteric cylinder remained expanded throughout the examination, failing to contract, and the pyloric orifice remained patent. The appearances were ascribed to a mass lesion, probably with ulceration, infiltrating the distal lesser curvature of the stomach and the first part of the duodenum. At endoscopy a deformity of the gastric "antrum", presumably due to external compression was seen, while the pyloric ring appeared normal. A large polypoid, lobulated mass measuring approximately 4.0 cm in diameter, was present in the duodenal bulb; the surrounding duodenal mucosa appeared normal. The biopsy specimen was inadequate but the possibility of malignant lymphoma was mentioned. Abdominal sonography showed no abnormality in the pancreas, liver, gall bladder and kidneys. Chest radiographs and bone marrow trephine biopsies were normal.

Fig. 34.2 Case J.J. Irregularity lower lesser curvature with ulcer-like projection. Pyloric sphincteric cylinder expanded. Pyloric aperture patent (arrow). Large, lobulated filling defect in duodenal bulb

At laparotomy two apparently separate mass lesions were found, one in the first part of the duodenum and the other in the distal stomach. Several enlarged perigastric lymph nodes were present. The liver and spleen appeared normal. Frozen sections suggested malignant lymphomatous disease, and a Billroth II partial gastrectomy was performed. Macroscopically the resection specimen showed several tumor nodules, varying in diameter from 1.5 cm to 4.0 cm, in the mucosa; some were ulcerated. The surrounding mucosa felt indurated. Microscopically the nodules consisted of mixed cellular infiltration; the majority of cells were of a lymphoid type while histiocytes, plasma cells and eosinophils were also present. Similar cells, as well as Reed Sternberg cells were seen in the lymph nodes. The condition was diagnosed as mixed cellularity Hodgkin's lymphoma.

Discussion #

Although primary malignant lymphoma may occur anywhere in the stomach, several authors commented on the fact that the pyloric region is the site most commonly affected (Naqvi et al l969; Meyers et al. l975; Lim et al. l977). It usually develops from lymphoid tissue in the mucosa (Ming l973), submucosa (Hricak et al. l980) or lamina propria (Sandler l984). In the early stages peristalsis may be impaired (Ngan and James l973), but it is usually not completely absent (Zornoza and Dodd l980), as the muscular layer is not infiltrated till a late stage (Sandler l984). In Case 34.1 radiographic examination showed widespread infiltration of the proximal part of the stomach, extending as far as the commencement of the pyloric sphincteric cylinder, which was in a state of partial contraction with absent cyclical activity; this is an uncommon presentation of malignant gastric lymphoma. In Case 34.2 there was radiographic and operative evidence of widespread involvement of the distal stomach, including the pyloric sphincteric cylinder and the first part of the duodenum, with destruction of normal anatomical features. The failure of cyclical activity of the sphincteric cylinder may be expected to hamper propulsion and trituration of solids.

Malignant gastric lymphoma has a definite tendency to extend across the pylorus into the duodenum (Meyers et al. l975; Hricak et al. l980; Craig and Gregson l98l); the spread usually occurs submucosally (Meyers et al. l975; Hricak et al. l980; Sandler l984), although mucosal spread has also been mentioned (Craig and Gregson l98l). Spread of gastric adenocarcinoma into the duodenum, although not as rare as postulated some decades ago, is less likely to occur (Chap. 33).

In one of 7 cases of duodenal spread of malignant gastric lymphoma, Meyers et al. (l975) noted that Brunner's glands were surrounded, but not invaded, by lymphomatous cells. (A possible relationship between pyloric adenocarcinoma and Brunner's glands of the duodenum is discussed in Chap. 33).

Whether malignant gastric lymphoma affects cells of the APUD system in the stomach is not known.

References