Symptomatic gastrointestinal metastases secondary to bronchogenic carcinoma

Clin. Radiol. (1978) 29, 217-225 SYMPTOMATIC GASTROINTESTINAL METASTASES SECONDARY TO BRONCHOGENIC CARCINOMA NORMAN JOFFE

Department of Radiology, Beth Israel Hospital and Harvard Medical School, Boston, Massachusetts, USA Gastrointestinal metastases secondary to bronchogenic carcinoma are relatively uncommon and most are found incidentally at autopsy examination in patients with advanced or widely disseminated lung cancer. Occasionally gastrointestinal metastases occur relatively early in the course of the disease and give rise to a variety of clinical symptoms and radiological abnormalities. Recognition of these abnormalities is important in order that appropriate palliative therapy may be undertaken. The clinical, radiological and pathological findings in 12 patients with symptomatic gastrointestinal metastases secondary to bronchogenic carcinoma were reviewed. Clinical symptoms varied according to the site of metastatic involvement and included dysphagia, epigastric pain, nausea, vomiting, gastrointestinal bleeding, anaemia and signs of intestinal obstruction or perforation. The sites of metastatic involvement were: oesophagogastric junction (2 cases); stomach (2 cases); duodenum (1 case); jejunum (3 cases); ileum (2 cases); colon (2 cases). The radiological findings are discussed and illustrated. Bronchogenic carcinoma which is currently the most common malignant neoplasm affecting the adult American male and increasing in incidence as a cause of cancer deaths in females (Silverberg and Holleb, 1974) is frequently associated with widespread dissemination of metastases (Galluzzi and Payne, 1955). Spread of bronchogenic carcinoma may occur by direct extension, lymphatic or haematogenous dissemination, bronchial intraluminal extension or implantation secondary to aspiration biopsy or surgery. While the biological behaviour of primary lung cancer depends on a number of factors, including cell type, location and immunologic response of the patient, its tendency to disseminate widely throughout the body is, in part, dependent on the rich lymphatic and vascular bed of the lungs. Apart from spread to regional lymph nodes which is extremely common, metastases most frequently involve the liver, adrenals, brain, bones and kidney (Table 1). Gastrointestinal metastases are relatively uncommon. In a review of 3047 autopsy cases collected from the literature Ochsner and DeBakey (1942) noted involvement of the gastrointestinal system in 4.3% (this figure does not include metastases to the pancreas or peritoneum which occurred in 7.3 and 4.8% of cases respectively). In 234 consecutive autopsies for primary lung cancer Engelman and McNamara (1954) found five (2.13%) with metastases in the intestines. Although only a small proportion of gastrointestinal metastases found at autopsy give rise to significant symptoms, recognition of the clinical and radiological abnormalities produced by such

metastases is important in order that appropriate therapy may be undertaken. Moreover, because of the increasing incidence of bronchogenic carcinoma, an increased incidence of gastrointestinal metastases may be anticipated. The present communication is concerned with a discussion and illustration of the radiologic abnormalities produced by gastrointestinal metastases secondary to bronchogenic carcinoma. MATERIAL AND METHODS The clinical, radiological and pathological findings in 12 patients with symptomatic gastrointestinal metastases secondary to bronchogenic carcinoma were reviewed. Diagnosis was established by endoscopy and biopsy, surgery or autopsy examination. There were nine males and three femalesg ages ranged from 49 to 76 years (mean, 60). Patients with dysphagia resulting from oesophageal involvement secondary to mediastinal lymphadenopathy or direct extension from a contiguous lung carcinoma were not included in this series. Also excluded were cases in which gastrointestinal symptoms occurred in association with diffuse peritoneal carcinomatosis. The sites of metastatic involvement were: oesophagogastric junction (2 cases); stomach (2 cases); duodenum (1 case); jejunum (3 cases); ileum (2 cases); colon (2 cases). In 10 of the 12 cases clinically manifest gastrointestinal metastases developed three months to two years after the initial diagnosis of bronchogenic carcinoma, while in two patients the primary lung cancer and symptomatic gastrointestinal

218

CLINICAL RADIOLOGY Table 1 - Incidence of exlxathoracic metastases from bronchogenie carcinoma at autopsy Author

Number of autopsies

Percentage incidence of metastases Liver

Adrenals

Brain

Bones

Kidneys

741

39.0

33_0

26.0

15.0

15.0

Ochsner & DeBakey 3047 (1942)

33.3

20.3

16.5

21.3

17.3

Spencer (1968)

38.5

26.4

18.4

15.5

14.3

Galluzzi & Payne (1955)

1000

Table 2 - Clinically manifest gastric metastases secondary to bronchogenic carcinoma Author

Location and cell type of primary lung tumour

Gastrointestinal Symptoms

Radiological Findings

Higgins (1962)

Undifferentiated squamous cell. Right upper lobe

Anorexia and vomiting

5 cm. submucosal pyloric mass

Simao (1963)

Squamous cell. Left upper lobe

Vague epigastnc pain; guaiac positive stools

Circumscribed ulcerated filling defect body of stomach

Dick & Pattinson (1972)

Poorly differentiated squamous cell. Right upper lobe

Anaemia

Two small polypoid lesions greater curve of body of stomach

Morten & Tedesco (1974)

Epidermoid. Left upper lobe

LUQ pain, anorexia and vomiting

2.5 cm. ulcerating mass on greater curve below oesophagogastric junction

Menuck & Amberg (1975)

Epidermoid. Left upper lobe

Epigastric pain, nausea and vomiting

Circumferential infiltrative lesion proximal body of stomach

metastases were discovered simultaneously. Clinical symptoms varied according to the site of metastatic involvement and included dysphagia, epigastric pain, nausea, vomiting, gastrointestinal bleeding, anaemia and signs of intestinal obstruction or perforation. The cell type o f the primary turnout was squamous cell (epidermoid) in six cases; anaplastic small cell ('oat cell') in four cases; adenocarcinoma in one case; undifferentiated large cell in one case. Apart from two cases in which metastatic involvement of the oesophagogastric junction resulted from lymphatic spread of the primary tumour, the presumed route of dissemination was haematogenous. DISCUSSION

Bronchogenic carcinoma is frequently associated with widespread dissemination and almost any por-

tion of the gastrointestinal tract may be the site of metastases with the production of a variety of clinical symptoms. Within the thorax displacement or compression of the oesophagus secondary to mediastinal lymphadenopathy or direct extension o f a contiguous lung neoplasm may give rise to dysphagia. Since the resultant radiologic abnormalities are well-known and the cause of the dysphagia is generally obvious, this type of secondary involvement will not be considered further. Intra-abdominal metastases may result from lymphatic spread of the primary tumour. Transdiaphragmatic lymphatics form an important link between the thoracic and abdominal l y m p h nodes and account for the relatively frequent occurrence of metastases in the intra-abdominal or retroperitoneal l y m p h nodes (Ochsner and DeBakey, 1942). With regard to secondary involvement o f the gastro-

SYMPTOMATIC G A S T R O I N T E S T I N A L M E T A S T A S E S

intestinal tract there is an important pathway of lymphatic drainage from the lower lobes of the lungs via the inferior pulmonary ligament and transdiaphragmatic trunks to juxta-aortic nodes and those around the abdominal segment of the oesophagus (Adkins, 1976; Rouvi~re, 1939). Involvement of this latter group of nodes may result in compression or encasement of the oesophagogastric junction region and give rise to dysphagia. In the case illustrated in Figure 1 dysphagia developed 11 months following resection of the right lower lobe for undifferentiated squamous cell carcinoma. The segment of narrowing in the region of the oesophagogastric junction was found at autopsy to be the result of encasement by metastatic lung carcinoma. In another patient with dysphagia and similar radiologic findings both the pulmonary and oesophagogastric lesions were demonstrated at the time of initial presentation and erroneously attributed to primary gastric carcinoma with a solitary pulmonary metastasis. Metastatic lesions in the stomach, small bowel and colon may result from haematogenous dissemination of bronchogenic carcinoma. Invasion of the lowpressure pulmonary veins by the primary lung turnout bypasses the "filtering barrier" of the pulmonary capillaries and provides ready access to the systemic arterial circulation. Although all histologic types of

219

Fig. 1 - 61 year old male complained of dysphagia 11 months after resection of right lower lobe for squamous cell carcinoma. (a) Tomographic section of right lower lobe showing large, circumscribed irregular mass. Barium meal examination at this time was normal. (b) Same patient 11 months later showing segment of narrowing with intact mucosa involving oesophago-gastric junction region. Autopsy revealed encasement by metastatic bronchogenic carcinoma.

bronchogenic carcinoma may spread by the bloodstream, the incidence of vascular invasion appears to vary with the cell type of the primary tumour (Gebarler, 1941; Koletsky, 1938). Anaplastic small cell ('oat cell') carcinoma frequently shows vascular invasion when first discovered and the peripheral adenocarcinoma of the lung is notoriously liable to spread in the same manner at a relatively early stage of growth (Spencer, 1968). On the other hand, the well-differentiated central squamous cell carcinoma spreads predominantly by regional lymphatics and vascular invasion tends to occur relatively late in the course of the disease. Gastric metastases secondary to bronchogenic carcinoma are relatively rare. Nevertheless, apart from malignant melanoma and breast cancer, bronchogogenic carcinoma is probably the commonest source of bloodborne gastric metastases (Davis and Zollinger, 1960; Higgins, 1962; Willis, 1973). The majority are found incidentally at autopsy examination in patients with advanced or widely disseminated lung cancer. Occasionally, however, gastric metastases occur relatively early in the course

220

CLINICAL RADIOLOGY

Fig. 2 - 66 year old female with epigastric pain and guaiac positive stools 19 m o n t h s after resection of left upper lobe for peripheral adenocarcinoma. (a) Tomographic section of left upper lobe showing irregular mass lesion with associated plate atelectasis. Barium m e a l examination at this time was normal. (b) Same patient 19 m o n t h s later showing ulcerated submucosal mass on lesser curve aspect of fundus of stomach. Endoscopy and biopsy revealed metastatic adenocarcinoma with histologic appearances identical to previous primary lung tumour.

of the disease and may give rise to clinically significant symptoms (Table 2). These include epigastric pain, anorexia, nausea, vomiting and evidence of gastrointestinal bleeding. Radiology plays the most important role in the initial detection of symptomatic gastric metastases. Bloodborne deposits are situated initially in the submucosa forming nodules or plaques which may enlarge and invade the mucosa resulting in polypoid masses with or without ulceration (Willis, 1973). Thus, barium studies typically reveal single or multiple, discrete submucosal masses or intraluminal filling defects with or without ulceration (Figs. 2B and 3). Small nonulcerated deposits may simulate benign gastric polyps (Dick and Pattinson, 1972). Localised or diffuse inf'dtration of the stomach wall ('linitis plastica'), which is the commonest radiologic manifestation of gastric metastases from breast cancer (Joffe, 1975) has not been obselned by the author in metastatic bronchogenic carcinoma; one such case has, however, been described in the literature (Menuek and Amberg, 1975). Since the radiologic differential diagnosis of gastric metastases from lung carcinoma

includes a relatively large number of conditions in which single or multiple, ulcerated or non-ulcerated nodules may occur, endoscopy and biopsy are generally required for confirmation of the diagnosis in order that proper therapy may be planned. In symptomatic patients this may consist of surgery for unassociated primary gastric lesions as opposed to non-surgical therapy (irradiation and/or chemotherapy) for metastatic disease. Small bowel and/or colon metastases may be asymptomatic and discovered incidentally at autopsy. The incidence of intestinal metastases from bronchogenic carcinoma is difficult to ascertain from the literature. In an autopsy study of 234 cases of lung cancer Engelman and McNamara (1954) found five (2.13%) with intestinal metastases. Simpson (19.29) examined 139 cases and found eight (5.7%) with intestinal metastases. Of 142 autopsy cases of discrete haematogenous small bowel metastases collected from the literature by Willis (1973), 17 were secondary to bronchogenic carcinoma. Clinically manifest intestinal metastases from lung cancer are

SYMPTOMATIC

GASTROINTESTINAL

Fig. 3 - 53 year old male with epigastric distress and haematemesis 3 m o n t h s after diagnosis o f anaplastic small cell ('oat cell') carcinoma right hilar region. Barium meal examination shows two large ulcerated polypoid mass lesions on greater curve aspect of antrum. E n d o s c o p y and biopsy confirmed diagnosis of metastatic 'oat cell' carcinoma.

uncommon. In two studies consisting of 40 symptomatic,small bowel metastases (excluding those due to direct extension or part of generalized peritoneal carcinomatosis) only one was secondary to bronchogenic carcinoma (DeCastro et al., 1957; Farmer and Hawk, 1964). It should be noted, however, that these studies were undertaken prior to the relative increase in incidence of primary lung cancer in the last decade, and in our experience symptomatic intestinal metastases are commoner than is generally recognized. Clinically, patients may present with evidence of intestinal obstruction (Barnard and Elliot, 1930), haemorrhage or perforation (Middell and Lochman, 1972; Morgan et aL, 1961; Ramanathan et aL, 1976; Tillotson and Douglas, 1962; Wootton et aL, 1967), and the onset of abdominal symptoms in any patient with known bronchogenic carcinoma should always raise the possibility of gastrointestinal metastases. Radiology plays an important role in the evaluation of such patients. Plain abdominal radiographs may reveal evidence of intestinal obstruction or free intraperitoneal gas secondary to perforation (Ramanathan et aL, 1976; Wootton et al., 1967). Barium studies usually show one of two types of abnormality. (1)

METASTASES

221

Fig. 4 - 58 year old male with upper abdominal pain, h y p o c h r o m i c anaemia and guaiac positive stools 15 m o n t h s after resection of s q u a m o u s cell carcinoma right upper lobe. Barium meal examination shows discrete, submucosal mass on lateral aspect of distal descending d u o d e n u m . Cytology and biopsy via endoscope positive for s q u a m o u s cell carcinoma.

Separation and angulation of bowel loops with contour defects and/or mucosal fixation secondary to metastatic mesenteric masses (Fig. 5A). This type of change was present in three of our 12 patients. The radiologic findings are identical to those seen with metastatic involvement of the mesentery and intestines from a wide variety of primary malignancies, especially those arising in the stomach, pancreas, colon and female genital tract. Secondary infiltration of the bowel wall along its mesenteric attachment may result in partial or complete intestinal obstruction (Fig. 5B). (2) Single or multiple discrete intramural mass lesions due to haematogenous submucosal deposits. These may be flat or polypoid in appearance (Figs. 4 and 6) and tend to occur on the anti-mesenteric margin of the bowel; rarely, localized submucosal intramural metastases are seen on the mesenteric border (Fig. 7). Obstructive symptoms may result from intussusception (Fig. 8B), or there may be evidence of gastrointestinal haemorrhage if there is associated mucosal ulceration. In general,

CLINICAL R A D I O L O G Y

222

Table 3 - Perforated small bowel metastases secondary to bronchogenic carcinoma Author

Primary lung tumour_

Metastatic small bowel lesion{s)

Predisposing factors

Morgan et al. (1961)

Anaplastic small cell. Left upper lobe

Perforated metastasis in jejunum 2 feet distal to ligament of Treitz

Intensive course of chemotherapy

Tillotson & Douglas (1962)

Carcinoma left lower lobe (cell type not indicated)

12 cm. necrotic metastasis communicating with ileum

Squamous cell. Left lower lobe

Perforated 8 cm metastasis in jejunum 22 cm distal to ligament of Treitz

Midell & Lochman (1972)

Undifferentiated 'giant cell' Right lower lobe

Perforated metastasis in ileum with generalised peritonitis

Ramanathan et aL, (1976)

Undifferentiated large cell. Right lower lobe

5 ulcerated metastatic nodules in jejunum with perforation of 2 nodules

Inalsingh et al. (1974)

Undifferentiated squamous cell Right upper lobe

3 metastatic nodules in terminal ileum with perforation of one

Wootton et al. (1967)

Radiation therapy to iliac bone metastasis

Fig, 5 - 62 year old male with abdominal pain and weight loss 2 years after diagnosis of squamous cell carcinoma left lower lobe. (a) Small bowel examination reveals separation and angulation of loops of proximal and mid small bowel with areas of mucosal fixation secondary to large mesenteric mass. (b) Same patient 5 month's later showinz almost total obstruction of proximal jejunum secondary to circumferential infiltration by metastatic turnout. Findings confirmed at autopsy.

SYMPTOMATIC GASTROINTESTINAL METASTASES

223

discrete submucosal haematogenous deposits tend to be commoner and more numerous in the small bowel than in the colon (Willis, 1973). Perforation of small bowel metastases from bronchogenic carcinoma is a rare but well-recognized phenomenon (Table 3). Clinically, patients may present with an acute abdominal episode requiring emergency surgery (Ramanathan, 1976; Wootton, 1967) or with more chronic symptoms and signs

suggestive of intra-abdominal inflammatory disease (Tillotson and Douglas, 1962). Plain abdominal radiographs may reveal free intraperitoneal gas; if barium studies are performed in less acute cases there may be evidence o f localised extravasation at the site o f tumour perforation (Fig. 9). Correct preoperative diagnosis is largely based on familiarity with this rare complication in patients with known bronchogenlc carcinoma. Although intensive chemotherapy or ab-

Fig. 6 - 76 year old female with undifferentiated large cell carcinoma of left lower lobe. Resection of lung turnout followed by gross tumour embolus in right femoral artery requiring emboleetomy. Six months later patient complained of abdominal cramps and diarrhoea. Barium enema examination which was normal at time of original lung surgery now revealed several large and small submucosal mass lesions in the descending colon. Similar deposits were present in the transverse colon.

Fig. 7 - 49 year old male with undifferentiated small cell carcinoma of left lung complained of left-sided abdominal pain and constipation_ Barium enema shows discrete submucosal intramural mass with mucosal fixation in middescending colon. Presence of metastatic mass confirmed at surgery.

224

CLINICAL RADIOLOGY

Fig. 8 - 69 year old female with squamous cell carcinoma of left main bronchus developed acute abdominal pain 2 days after bronchoscopy. (a) Chest radiograph shows collapse of left lung secondary to primary turnout. (b) Small bowel examination reveals intussusception in region of distal ileum. (c) Resected specimen of ileum showing large polypoid mass shown by microscopic examination to be metastatic squamous cell carcinoma.

f

I 8c

Fig. 9 - 60 year old male with known 'oat cell' carcinoma of the right lung presented with lower abdominal pain, fever, leucocytosis and tenderness in the right lower abdomen. Small bowel examination reveals irregular mass lesion in region of distal ileum with localised extravasation of barium. Surgery disclosed a large non-resectable inflammatory mass secondary to perforated metastatic 'oat cell' carcinoma in the ileum.

dominal irradiation have been proposed as possible predisposing factors in some cases (MideU and Lochman, 1972; Morgan et al., 1961), others have occurred spontaneously and it is likely that perforation is simply the result of destruction of the bowel wall by turnout growth and secondary ischaemia. Apart from involvement of the intestine by infiltrating mesenteric masses or discrete haematogenous deposits, small bowel lesions may occur as a result of gross tumour embolisation of the ' mesenteric arteries. Occasionally, lung carcinoma invades a major branch of the pulmonary veins, fills its l u m e n and extends along the vein towards the left atrium (Spencer, 1968). Detachment of a portion of the intravenous extension, which is especially liable to occur during surgical resection of the lung, may result in severe embolic complications (Aylwin, 1951). One of our patients developed gross tumour embolisation of the right femoral artery requiring

SYMPTOMATIC GASTROINTESTINAL METASTASES e m b o l e c t o m y a n d t h e a u t h o r has seen a case f r o m a n o t h e r i n s t i t u t i o n ( n o t i n c l u d e d in t h e p r e s e n t series) i n w h i c h gross t u m o u r e m b o l i s a t i o n o f t h e m e s e n t e r i c arteries f r o m a b r o n c h o g e n i c c a r c i n o m a r e s u l t e d in s e g m e n t a l i n f a r c t i o n o f t h e j e j u n u m .

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