Journal of Postgraduate Medicine Medknow Publications and Staff Society of Seth GS Medical College and KEM Hospital, Mumbai, India ISSN: 0022-3859 EISSN: 0972-2823 Vol. 49, Num. 1, 2003, pp. 83-84

Journal of Postgraduate Medicine, Vol. 49, No. 1, Jan-March, 2003, pp. 83-84

Images in Pathology

Isolated Splenic Metastases Occurring as an Unknown Primary Lesion

Alici S, Kosem M*, Kotan C**

Departments of Medical Oncology, *Pathology and **Surgery, Yuzuncu Yil University, School of Medicine, Van - 65200, Turkey.
Address for Correspondence: Suleyman Alici, Yuzuncu Yil Universitesi Tip Fakultesi, Arastirma Hastanesi Tibbi Onkoloji BD, Van / Turkey, 65200 E-mail: suleymanalici@yahoo.com

Code Number: jp03018

A 62-year-old female was referred for evaluation of enlarged spleen on physical examination. Abdominal examination revealed splenomegaly, the liver was not palpable, and rectal examination was unremarkable. Lactate dehydrogenase level was mildly elevated at 557 U/L (normal range, 240 U/L to 480 U/L). Results of other routine biochemical and hematologic tests were within normal ranges. The carcinoembryonic antigen (CEA) level was 19 ng/mL (normal, 0 ng/mL to 3.4 ng/mL).

Computed tomography (CT) of the abdomen and pelvis revealed an enlarged spleen containing a large solitary hypodense mass which had a lobulated contour. It showed no contrast enhancement. There was no evidence of internal soft tissue nodules or spotty calcifications. There was no evidence of extra-splenic extension or invasion of surrounding organs such as liver, retroperitoneum, and pelvic space. CT chest did not reveal any abnormalities. In the absence of any other metastatic lesions and, because it was believed that the splenic lesions would become symptomatic considering its size, the patient was advised to have a laparotomy for a possible splenectomy. At exploratory laparotomy, the spleen was found to be enlarged and its external surface was distorted. There were multiple enlarged splenic hilar lymph nodules. The liver, colon, and other viscera were normal. Splenectomy was done without complications, and the post-operative course was uneventful. The spleen was 1500 g in weight and measured 20x 15.6x 6.2 cm, the cut surface revealed a necrotic, haemorrhagic, cavitary lesion 7cm in diameter. The edges of the lesion showed beige coloured irregular, solid areas. Histopathologic examination revealed pleomorphic tumour cells with moderate cytoplasm. The tumour cell groups were arranged in solid, trabecular, alveolar and acinar pattern (Figure 1) and poorly differentiated glandular pattern in tumor tissue (Figure 2). Immunohistochemical stains were performed for cytokeratin, neuron-specific enolase (NSE), chromogranin, and hormone receptors for invasive ductal carcinoma on formalin-fixed tissue. Tumor cells displayed strong cytoplasmic staining for cytokeratin, but no staining with NSE, chromogranin and hormone receptors. Primary tumor was suspected to be localized in pancreas, breast, colon, ovary or fallopian tubes based on histopathological examination. The case was reported as metastating poorly differentiated adenocarcinoma. Combination chemotherapy regimen (PF) consisting of cisplatin 75 mg/m2/day, on day 1 and 5-fluorouracil 600 mg/m2 /day, on days 1 to 5, intravenous every 4 weeks was initiated post-operatively. She received six courses of PF. No primary lesion was identified even in post-operative survey. The post-operative course was uneventful with no evidence of recurrence six months after the operation. At 4-month follow-up, the patient was asymptomatic, with a CEA level of 0. The CT of the abdomen showed no persistence or recurrence of disease.

Discussion

Prior large studies of splenic metastases were limited to autopsy series^1,2 as ante-mortem diagnosis was rarely achieved. Only sporadic individual case reports of splenectomy for metastases existed before 1987.³ Although only an autopsy series can identify the true frequency of splenic metastases in cancer patients, many of these metastases detected at autopsy may have been silent clinically. Splenic metastases are found with a frequency varying from 2.4 to 7.1%. The malignancies of the breast, lung, and pancreas, and malignant melanoma are the commonest cancers that metastasise to other organs.⁴ Splenic metastases from a primary tumour of any source are usually a part of widespread metastatic disease and are reported at autopsy, with an incidence of 7%.⁵ Spontaneous splenic rupture and consequent haemorrhage is a rare complication of these tumours.⁶ In the presence of large splenic deposits, a splenectomy may be justified to avoid the potential catastrophic event of splenic rupture. Because of the high likelihood of widespread metastases, routine resection of the primary tumour may not be justified.

The spleen is full of immunologically competent cells such as lymphoid tissue and Kupffer's cells, which may hinder the establishment of metastatic disease. An experimental study showed that the liver supported the uptake of transplantable mouse tumour cells, whereas the spleen appeared to retard this phenomenom.⁷ A clinical study using radio-colloid imaging found that the rate of growth of splenic metastases was less than that observed for intra-hepatic metastases.⁸ This phenomenon is probably related to the "immunologic surveillance" carried out by the spleen and it explains the apparent "poor soil" that spleen offers for tumour implantation. It is possible that the spleen produces several factors that inhibit tumour implantation and tumour growth. O'Reilly et al⁹ described an anti-angiogenesis factor (named angiostatin) in an experimental model of murine lung cancer that was shown to interfere with tumour angiogenesis, which is an important component of tumour expansion and metastatic spread.

References

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2. Berge T. Splenic metastases. Frequencies and patterns. Acta Pathol Microbiol Scand 1974;82:499-506.
3. Hulbert JC, Graf R. Involvement of the spleen by renal angiomyolipoma: Metastasis or multicentricity? J Urol 1983;130:328-9.
4. Vadala G, Caragliano L, Castorina R, Caragliano V, Caragliano P. Splenic metastases. Minerva Chir 1999;54:273-6.
5. Marymount JH Jr, Gross S. Patterns of metastatic cancer in the spleen. Am J Pathol 1963;40:58-60.
6. Gupta PB, Harvey L. Spontaneous rupture of the spleen secondary to metastatic carcinoma. Br J Surg 1993;80:613.
7. Miller JN, Milton GW. An experimental comparison between tumour growth in the spleen and liver. J Pathol Bacteriol 1965;90:5515-21.
8. Spencer RP. Intrasplenic metastases: radio-colloid studies of growth rate, response to therapy and possible splenic "immunity". Invest Radiol 1980;15:379.
9. O'Reilly MS, Holmgren L, Shing Y, Chen C, Rosenthal RA, Moses M, et al. Folkman J. Angiostatin: a novel angiogenesis inhibitor that mediates the suppression of metastases by a Lewis lung carcinoma. Cell 1994;79:315-28.

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