Malignant gastric stromal tumor: unusual metastatic patterns. (Case Report).

Abstract: We present the case of a woman with metastatic malignant gastric stromal tumor occurring four years following a partial gastrectomy and distal esophagectomy, which presented as atypical breast mass with synchronous occult gastrointestinal bleeding. A discussion of metastatic pattern is presented, with emphasis placed on the need for continued surveillance after resectional surgery for gastrointestinal stromal tumor (GIST).

Key Words: gastrointestinal stromal tumor, leiomyoblastoma, lymph node metastasis

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Key Points

* Gastrointestinal stromal tumors were originally described as leiomyomas or leiomyoblastomas involving the smooth muscle of the gastrointestinal tract.

* Patients with gastrointestinal stromal tumors usually present with obstructive symptoms or gastrointestinal bleeding.

* The mode of metastasis is commonly hematogenous, with spread to the lungs, liver, and, rarely, to the lymph nodes.

* Surgical resection with clear margins remains the preferred method of treatment.

* Consistent long-term surveillance after surgical resection is required because the malignant potential of gastrointestinal stromal tumors is unpredictable.

Gastric stromal tumor is a rare entity. It accounts for a small percentage of smooth muscle tumors of the stomach. Management usually consists of excision of the tumor with a good margin of normal tissue. Wide resection of lymph node areas is not indicated because of the extreme rarity of lymph node metastasis. (1,2) The most common site of metastasis of malignant stromal tumor is the liver, peritoneum and lung. These can develop as long as thirty years after the removal of the primary tumor. In this report, we describe the metastasis of a gastric stromal tumor to an intramammary lymph node and synchronous small bowel metastasis four years after primary gastric resection. A review of the literature and the pattern of metastasis are discussed.

Discussion

Stromal tumors of the gastrointestinal tract represent the largest category of primary nonepithelial neoplasms of the stomach and small bowel. They are believed to arise from stromal cells located within the walls of the organ. For years, these lesions were regarded as smooth muscle tumors and designated as leiomyomas and leiomyosarcomas when composed of spindle cells and as benign or malignant leiomyoblastomas when composed of epithelioid cells. (3) Immunohistochemical studies of these tumors have revealed differentiation (4) along various pathways, including smooth muscle, neural, both or neither. Interestingly, and of practical importance, the histochemical differentiation markers have helped to subdivide these tumors into categories with distinct prognostic differences. All tumors that show differentiation toward neural elements, for example, are currently regarded as malignant. Furthermore, tumors which exhibit dual differentiation toward smooth muscle and neural or which display neither, are considered to be either malignant or potentially malignant. By contrast, tumors that display only smooth muscle differentiation can be divided into either benign, borderline or malignant depending on several features, chief of which are mitotic rate and tumor size. Features which favor malignancy include size larger than 5 cm, necrosis, hemorrhage, hypercellularity, nuclear atypia, mitoses greater than 5 per 50 HPFs and location in the proximal anterior wall of the stomach. (5,6)

Even with the improvement brought about by immuno-histochemical analysis, the biologic behavior of these tumors may still be unpredictable. These tumors tend to be well circumscribed with sharp peripheral boundaries with occasional presentation as slightly lobulated masses. Only rarely do they appear to invade another organ such as the liver, spleen or pancreas. Benign tumors become adherent to these organs, although there is no invasion.

The risk of metastasis is a function of the size of the tumor. (1) The larger the tumor, the greater is the metastatic risk though small tumors as tiny as 2 cm in maximal diameter metastasize on occasion. In some other studies, metastasis is related to the mitotic count. (6,7) Metastases are often present at the time the primary tumor is discovered in 15 to 27% of cases. (8) These are related to the rapidity and accuracy of clinical diagnosis, particularly for those patients with long duration of symptoms. Metastases usually become clinically apparent within the first 18 to 24 months after diagnosis, though they can develop as long as 30 years after the removal of the primary tumor. (9) The most common metastatic sites are the peritoneal surfaces and liver, followed by retroperitoneal soft tissues. (6,7,9,10) They tend to stay inside the abdomen. Intraabdominal recurrences generally become clinically apparent less than two years after initial resection. The small bowel recurrence reported in this case could most likely be related to tumor spillage from handling during the resectional surgery four years prior. This small bowel recurrence/metastasis was resected with a small margin (6 cm) because there is no evidence in the literature that suggests improved results or better survival with greater resection margins. (2,6,7,11)

Lymph node metastases for gastric stromal tumor are unusual, (12) occurring in about 5% of patients. They are usually intra-abdominal or within the lymph nodal region of the primarily involved organ. Extra-abdominal metastasis such as to lung and bone occur in approximately 10% of patients. (1,2) To our knowledge, no cases of extra-abdominal lymph node involvement has been described, especially to the breast, which has no direct lymphatic connection with the stomach. Both the small bowel and intramammary metastasis were resected. Resection of recurrent tumors or metastases has been advocated, because they are slow growing and long-term survival has been reported in many cases. (9,13) Long-term survivors are usually women (80%) in whom tumors develop at a young age. In this patient, no further therapy was given after surgical resection. There is as yet no established value for adjuvant chemotherapy or radiotherapy.

Malignant gastric stromal tumors are rare and can metastasize to the liver, peritoneum, and lungs, and rarely to the lymph nodes. (14-16) All of these metastases may be amenable to surgical resection as the primary therapy. The reported case helps to illustrate the unpredictable biologic nature and metastatic potential of malignant gastric stromal tumor. It reaffirms the need for consistent long-term follow-up after oncologic surgical therapy.

Accepted November 16, 2001.

References

(1.) Appelman HD, Helwig EB. Gastric epithelioid leiomyoma and leiomyosarcoma (leiomyoblastoma). Cancer 1976;38:708-728.

(2.) Shiu MH, Farr GH, Papachristou DN, Hajdu SI. Myosarcomas of the stomach: Natural history, prognostic factors and management. Cancer 1982;49:177-187.

(3.) Enzinger FM, Lattes R, Torloni H. Histological typing of soft tissue tumours (International Classification of Tumours No. 3). Geneva, World Health Organization, 1969.

(4.) Erlandson RA, Klimstra DS, Woodruff JM. Subclassification of gastrointestinal stromal tumors based on evaluation by electron microscopy and immunohistochemistry Ultrastruct Pathol 1996;20:373-393.

(5.) Appelman HD. Stromal tumors of the esophagus, stomach, and duodenum, in Appelman HD (ed): Pathology of the Esophagus, Stomach, and Duodenum. New York, Churchill Livingstone, 1984, pp 195-242.

(6.) Appelman HD, Helwig EB. Sarcomas of the stomach. Am J Clin Pathol 1977;67:2-10.

(7.) Dougherty MJ, Compton CC, Talbert M, Wood WC. Sarcomas of the gastrointestinal tract: Separation into favorable and unfavorable prognostic groups by mitotic count. Ann Surg 1991;214:569-574.

(8.) Farrugia G, Kim CH, Grant CS, Zinsmeister AR. Leiomyosarcoma of the stomach: Determinants of long-term survival. Mayo Clin Proc 1992; 67:533-536.

(9.) Ng EH, Pollock RE, Romsdahl MM. Prognostic implications of patterns of failure for gastrointestinal leiomyosarcomas. Cancer 1992; 69:1334-1341.

(10.) Ranchod M, Kempson RL. Smooth muscle tumors of the gastrointestinal tract and retroperitoneum: A pathologic analysis of 100 cases. Cancer 1977;39:255-262.

(11.) Grant CS, Kim CH, Farrugia G, Zinsmeister A, Goellner JR. Gastric leiomyosarcoma: Prognostic factors and surgical management. Arch Surg 1991; 126:985-990.

(12.) Lee JS, Nascimento AG, Farnell MB, Carney JA, Harmsen WS, Ilstrup DM. Epithelioid gastric stromal tumors (leiomyoblastomas): A study of fifty-five cases. Surgery 1995;118:653-661.

(13.) Persson S, Kindblom LG, Angervall L, Tisell LE. Metastasizing gastric epithelioid leiomyosarcomas (leiomyoblastomas) in young individuals with long-term survival. Cancer 1992;70:721-732.

(14.) Ballarini C, Intra M, Ceretti AP, Prestipino F, Bianchi FM, Sparacio F, et al. Gastrointestinal stromal tumors: A "benign" tumor with hepatic metastasis after 11 years. Tumori 1998;84:78-81.

(15.) Rosai J. Gastrointestinal tract: Stromal tumors, in Rosai J (ed): Ackerman's Surgical Pathology. St. Louis, Mosby, 1996, ed 8, pp 645-648.

(16.) Appelman HD, Lewin KJ. Mesenchymal tumors and tumor-like proliferations, in Lewin KJ, Appelman HD: Atlas of Tumor Pathology: Tumors of the Esophagus and Stomach. Washington, DC, Armed Forces Institute of Pathology, 1997, vol 18, 3rd series, pp 405-456.

RELATED ARTICLE: Case Report

A 64-year-old woman with no family history of breast cancer was referred for evaluation of a palpable left breast mass that was recently noticed on breast self-examination. The medical history was significant for proximal gastrectomy four years prior for malignant stromal tumor of the gastric fundus. At the time or surgery, there was no evidence of metastatic disease. Thirteen perigastric lymph nodes and the spleen were negative for metastatic disease. Periodic surveillance esophago-gastroduodenoscopy (EGD) has remained negative.

Physical examination revealed a 1.5-cm mass in the upper outer quadrant of the left breast, which was freely mobile with no palpable axillary lymph nodes. A mammogram demonstrated the interval appearance of a macrolobulated 1 cm intramammary mass in the posterior one-third of the left breast at 12 o'clock position (Fig. 1, A and B). Open excision biopsy of the mass revealed a single intramammary lymph node measuring 0.65 cm in diameter. Pathology revealed subtotal replacement by a metastatic tumor composed of epithelioid cells resembling the original gastric tumor cells (Fig. 2, A and B). Immunohistochemical studies were performed on the lymph node metastasis that supported the interpretation of metastatic stromal tumor with strongly positive vimentin and completely negative cytokeratin staining studies.

While a metastatic workup was in progress, the patient developed weakness and dizziness on standing. Further examination then revealed pallor, no abdominal masses or distension and guaiac positive stools with hemoglobin of 6.9 g/dl. Workup with EGD showed no evidence of disease recurrence in the stomach or anastomosis. Colonoscopy to the ileocecal valve was unrevealing except for guaiac positive effluent at the terminal ileum. Enteroscopy was normal to about 30 cm beyond the ligament of Treitz. A small bowel follow-through (SBFT) then revealed a spherical mass compressing and distorting the lumen of the small bowel in the left lower quadrant (Fig. 3). A follow-up CT scan of the abdomen demonstrated a 3-cm partially necrotic solid mass in the mesenteric border of the mid-portion of the small bowel, stretching and narrowing the bowel lumen (Fig. 4).

The patient was then taken to the operating room for exploratory laparotomy, which revealed a nearly obstructing distal jejunal mass with serosal adhesions and kinking of the adjacent small intestine. The mass and adherent small bowel was resected with 6 cm. proximal and distal margins. No further evidence of intra-abdominal disease or liver involvement was noted. Patient did well postoperatively and was subsequently discharged home on postoperative Day 7. Gross examination of the small bowel segment revealed a solitary well-circumscribed tan, partially hemorrhagic mural mass lesion measuring 4 cm in greatest dimension and extending from the submucosa to the serosa. The histology of the small bowel tumor (Fig. 20) was similar to the gastric primary but more poorly differentiated and with more mitoses than the gastric tumor (up to 15 per high-power field). The pathologic interpretation was "malignant stromal tumor, probably metastasis from gastric primary" although a new small bowel primary could not be exclud ed completely (Fig. 2).

From the Departments of General Surgery, Radiology, and Pathology, St. Francis Hospital, Evanston, IL.

Reprint requests to Obinna C. Igwilo, MD, FRCS (Edin), FRCPS (Glasgow), Carolina Surgical Specialists, PA, 307 N. Greene Street, Wadesboro, NC 28170.

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