Uncommon mucosal metastases to the stomach

Primary gastric cancer is the second highest cause of global cancer mortality accounting for over 700,000 deaths annually [1]. Gastric cancer is curable if it is detected early; however many patients are diagnosed with late stage disease wherein despite advances in management protocols, current therapeutic strategies still remain far from optimal [2, 3]. Current strategies including surgery and combination chemotherapies provide modest survival benefits in advanced gastric cancer resulting in an overall 5 year survival rate less than 24% [4, 5].

Secondary gastric cancer however is a rare event and remains a challenging clinical problem [6, 7]. The most commonly described primary sites are breast, melanoma and lung [8, 9]. The recognition of such metastases to the stomach outside of findings at autopsy is rare [10]. Higgins found 64 cases of metastatic carcinoma in the stomach among 31,541 autopsied cases while Davis and Zollinger reported 67 metastatic tumours in the stomach among 23,109 autopsied cases [11, 12]. However, with enhanced overall survival of these patients these lesions are also being diagnosed with the increased use of esophagogastroduodenoscopy [13].

The clinical presentation of upper gastrointestinal bleeding as a manifestation of gastric metastases is unusual. Further, gastrointestinal bleeding due to secondary gastric choriocarcinoma is uncommon [14]. Metastases to the stomach from a testicular germ cell tumour is extremely rare though autopsy findings indicate a much higher incidence [15]. We will now share our experience of three uncommon metastases to the stomach recognized by histopathological examination of mucosal biopsies obtained at upper gastroendoscopy.

The involvement of the stomach by metastases is rare with the most common reported primaries include melanoma, and carcinomas of the breast and lung [7, 16]. The estimated incidence of gastric metastases at autopsy in individuals with a known malignancy varies from 1.7% [17] to 5.4% [Oda [10]]. Up to half of individuals harbouring such metastases are symptomatic, most commonly with bleeding, pain, vomiting and anorexia [18].

Choriocarcinomas of the testis account for only 0.3% of testicular tumours [19], and gastric involvement by primary testicular germ cell tumour is extremely rare [14, 15, 20]. Aydiner et al claim the first report of choriocarcinoma metastatic to the stomach in 1993.[21] Testicular choriocarcinoma is most commonly identified in patients in their second and third decades presenting with varied symptoms including hemoptysis, lumbar back pain, GI bleeding, neurological symptoms and endocrinological abnormalities [22]. Choriocarcinomas in particular have a marked affinity for angioinvasion, and disseminate rapidly, disproportionately frequently to the brain [15]. As would be expected from the clinical presentation, it is estimated that half of the patients with testicular germ cell tumours will have metastases at diagnosis, with the most common destinations being, in addition to the brain, the lymph nodes, liver, and lung [14]. Metastases are relatively uncommon to the GI tract, spleen and adrenals [17]. Typically, these lesions respond promptly to chemotherapeutics, and for this reason it is essential to identify metastases to the GI tract, and surgically resect these if feasible. Occasionally, the therapeutic response of the lesion to chemotherapy may result in haemorrhage or intestinal perforation [23]. As primary gastric choriocarcinoma has also been described, an additional diagnostic conundrum for the pathologist involves evaluation of whether the gastric mucosal biopsy represents a primary or a 'true' secondary lesion from an occult testicular primary. While the initial presentation, often dramatic, will draw clinical attention to the metastasis rather than the primary, the accurate diagnosis hinges upon awareness that the gastric lesion could be metastatic, and proceed with a full clinicopathological evaluation to include/exclude a silent testicular primary.

Adenocarcinoma of the lung is now the most frequent form of lung carcinoma in the United States [24], most frequently seen in non-smokers and females. This tends to be a peripherally located lesion, and consequently patients demonstrate late symptoms related to the increasing size of the tumour, distant metastases, and invasion of the pleural compartment. Lymphatic and hematogenous metastases are common, and adenocarcinoma of the lung has the highest incidence of intrapulmonary metastasis [25]. Likewise, adenocarcinoma is the most frequent form of lung carcinoma observed to yield gastric metastases [9, 26]. As observed with testicular primaries, acute upper gastrointestinal bleeding and gastric perforation secondary to metastatic lung adenocarcinoma following systemic chemotherapy have been reported [27, 28]. It is essential not to forget the possibility of metastatic disease in the differential diagnosis of the patient presenting with a gastric lesion [29] This is further complicated by the fact that adenocarcinoma metastatic to the lung may be virtually indistinguishable from primary gastric adenocarcinoma at histopathological evaluation. Kim et al reported a case of metastatic poorly differentiated carcinoma which, radiologically and endoscopically, was featured like polypoid primary gastric carcinoma [7]. Further to compound the problem, the primary lung adenocarcinoma may not be readily apparent, as in Yamamoto et al's report of lung adenocarcinoma metastatic to the stomach, in which the 4-cm primary tumour in the left lung was not detectable on plain X-ray [30]

Colonic adenocarcinoma is the second most common cause of cancer mortality in North America [31]. Lymphatic and hematogeous metastases to the liver typically occur once the submucosa has been invaded by the way of the portal venous system. While 20% of patients have distant metastases at diagnosis, gastric metastases resultant from colon cancer has been reported infrequently [9, 10].

The appearance of metastases to the stomach at endoscopy is variable. The appearance on imaging or gross inspection is generally not suggestive of the primary. Gastric involvement may be characterized by a single lesion in the gastric body or by multiple lesions [6, 10]. Often the lesion is described as a "volcano-like" ulcer [18]. The metastases may have the clinical appearance of a primary stromal gastric tumour [19]. Since metastases to the stomach can present before the primary malignancy declares itself, there is danger of mistaking these metastases for primary gastric cancer, and consequently failing to recognize the true primary. Of particular interest to the pathologist is that adenocarcinomas of gastrointestinal or pancreatobiliary origin may adhere to the gastric glands and pits, preserving this morphology even as pits themselves are destroyed mimicking an in-situ 'pseudoprimary' gastric lesion. Similarly, malignancy metastatic from the breast may illicit marked desmoplasia within the stomach so as to convincingly simulate linitis plastica [19].

Gastric metastases may be recognizable as abnormalities on gastroscopy; however as the morphology is variable there are no characteristic appearances that define metastatic disease [10]. Likewise, the appearance on CT scans of metastatic neoplasms to the stomach are indistinguishable from that of gastric primary malignancies, such as adenocarcinoma or lymphoma, and can also be easily confused with the appearance of food residue or inadequate gastric distension. On barium X-ray, these lesions often are described as "target lesions" with the lesion itself depicted as a filling defect and a central collection of barium within it, likely related to the ulcerated morphology seen endoscopically. Frequently, bridging mucosal folds are noted which suggest a submucosal mass. Unfortunately, this "bulls' eye" lesion is also in keeping with a multitude of neoplastic and non-neoplastic conditions of the stomach, including lymphoma, carcinoid, Kaposi's sarcoma and gastric ulcers [32].

In conclusion as pitfalls abound in the clinical presentation, diagnostic imaging and histopathology, it is essential to be acutely aware of both common and uncommon metastases to the stomach and to appropriately include these in the differential diagnosis of all gastric lesions for accurate diagnosis and optimal patient management.

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