Solitary recurrent metastasis of squamous cell carcinoma of the uterine cervix in the spleen: case report.

Abstract: In cervical squamous cell carcinoma, solitary metastasis to and recurrence in the parenchyma of the spleen are uncommon in the absence of apparent disease in other sites. A case of a 50-year-old patient with a Stage IIa carcinoma of the cervix treated with radical hysterectomy and pelvic lymphadenectomy followed by radiotherapy is reported. Serial squamous cell carcinoma (SCC) antigen measurements have been performed for monitoring the course of disease, response to treatment, and detection of tumor recurrence. Recurrent disease was initially suspected on the basis of an elevated SCC level, 7.11 [micro]g/ml (normal, < 1.5 [micro]g/ml), subsequently confirmed by computed tomographic scan, magnetic resonance imaging, and positron emission tomography of the abdomen and pelvis. Laparoscopic splenectomy followed by chemotherapy with cisplatin was performed. The SCC antigen level was within normal limits postoperatively. The patient was well and clinically free of disease for 5 months.

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Squamous cell carcinoma (SCC) antigen level testing has been investigated in patients with invasive cervical cancer for the past two decades. Over 50% of patients with invasive cervical cancer have been reported to have elevated serum SCC antigen levels at the time of diagnosis; serial levels have been shown to correlate with tumor response of advanced disease to radio- or chemotherapy. (1,2) The most important use for SCC antigen in SCC of the cervix is its ability to monitor disease after treatment and accurately predict recurrence. (3,4)

SCC of the uterine cervix most commonly metastasizes in a stepwise fashion to adjacent tissues and lymphatics. Disease usually metastasizes to pelvic and para-aortic lymph nodes before spreading to distant organs. Reported sites of distant metastasis include the lung, bone, liver, and mediastinal and supraclavicular lymph nodes. Most commonly, metastases to the spleen, of which only 22 cases have been described in the world literature, are associated with widespread tumor dissemination throughout the abdominal cavity and/or other organ parenchyma. Isolated solitary parenchymal metastases in the spleen are rare, especially in recurrent disease. To the best of my knowledge, only one case has been described in the literature. (5) A patient who developed a solitary metastatic lesion in the spleen 5 years after completion of primary treatment for a Stage IIa SCC of the cervix is reported.

Case Report

A 45-year-old woman presented to the Chang-Gung hospital with a 2-month history of postcoital bleeding and a few episodes of spontaneous intermenstrual vaginal bleeding. Colposcopic examination revealed a mass in the cervix that was 4.5 cm in maximum diameter. A cervical biopsy was performed and the pathologic examination showed a moderately differentiated SCC. Chest radiography, intravenous pyelography, cystoscopy, and rectosigmoidoscopy were normal. Computed tomographic (CT) scan of the abdomen and pelvic cavity was essentially unremarkable. SCC antigen determination was not performed. The clinical diagnosis was an International Federation of Gynecology and Obstetrics Stage IIa lesion. Radical hysterectomy with bilateral pelvic lymphadenectomy was performed. Pathologic examination revealed a moderately differentiated SCC of the cervix with involvement of the vaginal cuff. The uterine corpus, bilateral adnexae, and all lymph nodes dissected were negative for malignancy. Postoperative prophylactic radiotherapy was performed.

The patient was followed with SCC antigen testing for monitoring the course of disease and response to treatment. Assays were performed at 3-month intervals during the first 2 years and subsequently at 4- to 6-month intervals. The results of SCC antigen level were less than 3.5 ng/ml with slowly progressive elevation in the past 5 years (Fig. 1). The patient remained free of disease with no evidence of any clinical symptoms. Thereafter, recurrence was first suspected because the serum SCC antigen level increased above the normal range (7.11 ng/ml) and subsequently was confirmed by CT scan, magnetic resonance imaging (MRI), and positron emission tomography (PET).

MRI after IV contrast injection showed a heterogeneously enhanced tumor mass in the dorsal aspect of the spleen with transcapsular extension (Fig. 2). Abdominal CT scan revealed a splenic nodule (Fig. 3). CT scan of the pelvis showed no evidence of tumor recurrence and no enlargement of para-aortic, pelvic, and inguinal lymph nodes. Chest CT scan was unremarkable. PET with F-18 2-deoxyglucose whole-body scan at 40 minutes after injection of 9.2 mCi of F-18 2-deoxyglucose revealed a focal area of increased uptake of radioactivity in the splenic area (Fig. 4). There was no other abnormal area of increased uptake of radioactivity in the head, neck, chest, and pelvic region. Laparoscopic splenectomy was performed.

Gross pathologic examination revealed a spleen measuring 16.5 X 7.5 X 4.5 cm and weighing 210 g (Fig. 5) and a yellowish-white mass measuring 5.5 X 3.7 X 3.5 cm in the splenic parenchyma with transcapsular extension to the splenic hilus. Microscopic examination revealed a metastatic moderately differentiated SCC in the splenic parenchyma with extension to the hilus (Fig. 6).

Postoperative prophylactic chemotherapy with cisplatin was performed. After the splenectomy, the SCC antigen level returned to within the normal range. The patient remained free of clinical and radiologic evidence of disease for 5 months.

Discussion

The spleen is considered unfavorable to the development of metastasis, but the reason for this is not fully understood. There are three possible routes for spread of tumor to the spleen: by means of the splenic artery, retrogradely by means of the splenic vein, and through the lymphatics. Metastatic carcinoma that involves the spleen is usually a clinical manifestation of widely disseminated disease involving multiple organs. Isolated solitary parenchymal metastases in the spleen are rare.

The treatment of carcinoma of the uterine cervix over the past decades by radiotherapy and surgical techniques has led to increased survival rates and has permitted more widespread metastases to become clinically evident. The literature contains relatively few series reporting on splenic metastases. Large systemic clinicopathologic studies that give an actual account of this condition are lacking. The most impressive publication to date regarding this matter is that of Carlson et al, (6) who reviewed 2,200 cases treated for SCC of the cervix and did not find any metastatic lesion to the spleen. Sotto et al (7) analyzed the autopsy protocols of 108 cases of carcinoma of the cervix and found eight cases of spleen involvement. Badib et al (8) studied a series of 227 cases of cancer of the cervix and found only 13 cases with spleen metastasis. Recently, Lam and Tang (9) reviewed clinical/autopsy records of 92 patients with malignant tumors from different sites and reported only one case of SCC of the cervix with splenic metastasis. It was not stated whether the spleen was the only site of involvement in those reports. There is only one case report of SCC of the cervix with isolated solitary recurrence in the spleen, diagnosed clinically as the only documented site of distant metastasis. (5)

Cervical SCC with metastasis to the spleen has been reported previously. In addition to clinical history and physical examination, routine follow-up screening with radiologic imaging such as CT scanning, MRI, or bone scan, or vaginal cytologic studies were performed to detect any evidence of tumor recurrence or metastasis. In the current case, monitoring SCC antigen levels for recurrence was performed, and this is the first case using the SCC antigen level to detect solitary metastasis to the spleen.

It should be acknowledged that recurrent disease is in fact the ultimate clinical manifestation of the growth of metastasized tumor cells that were already present at admission and that routine diagnostic procedures have failed to detect. SCC antigen measurements might be useful for monitoring this disease, provided that the recurrence of the disease can be detected early and accurately by this method. By far the most important role for SCC antigen testing in the management of cervical cancer is its potential for monitoring the clinical course of disease and response to treatment. (1-4) In the current case, postoperative radiotherapy and chemotherapy were performed to prevent recurrent disease resulting from the growth of microscopically residual tumor or subclinically metastasized tumor cells. Serial SCC antigen testing has been proven to be more specific than sensitive. (10) In multiple studies, the average lead time between the first elevated SCC antigen level and clinical detection of recurrent cervical cancer was found to be approximately 6 months. (10) Clearly, SCC antigen monitoring is predictive of recurrence significantly before the appearance of clinical symptoms in many selected patients as in the current case. Furthermore, highly sensitive imaging techniques such as CT scan, MRI, and PET can specifically detect definite recurrence in response to elevated SCC antigen levels.

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Although SCC antigen measurement helps to predict recurrent disease, it does not alter the clinical management of recurrent disease. Treatment of recurrent carcinoma of the cervix depends on the site and extent of disease by the time the diagnosis is made.

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For the present case with isolated parenchymal splenic metastasis from recurrent cervical cancer, a laparoscopic splenectomy may play an important role and may lead to a prolonged disease-free interval. The role of laparoscopy in assisting in the identification and resection of this specific patient with solitary recurrence may prove beneficial.

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Conclusion

A case of isolated solitary metastasis to and recurrence in the parenchyma of the spleen by SCC of the uterine cervix is presented. Recurrent disease was initially suspected on the basis of an elevated SCC antigen level and subsequently confirmed by CT scan, MRI, and PET of the abdomen and pelvis. Laparoscopic splenectomy was performed and followed by chemotherapy with cisplatin. The patient has remained without further evidence of disease for 5 months.

Accepted April 23, 2003.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9703-0301

References

1. Ngan HY, Wong LC, Chan SY, et al. Use of serum squamous cell carcinoma antigen assays in chemotherapy treatment of cervical cancer. Gynecol Oncol 1989;35:259-262.

2. Ngan HY, Chan SY, Wong LC, et al. Serum squamous cell carcinoma antigen in the monitoring of radiotherapy treatment response in carcinoma of the cervix. Gynecol Oncol 1990;37:260-263.

3. Brioschi PA, Bischof P, Delafosse C, et al. Squamous cell carcinoma antigen (SCC-A) values related to clinical outcome of preinvasive and invasive cervical carcinoma. Int J Cancer 1991;47:376-379.

4. Holloway RW, To A, Moradi M, et al. Monitoring the course of cervical carcinoma with the squamous cell carcinoma serum radioimmunoassay. Obstet Gynecol 1989;74:944-947.

5. Carvalho L, Azevedo I, Salgado L, et al. Squamous cell carcinoma of the cervix metastatic to the spleen: Case report. Gynecol Oncol 1997;67:107-110.

6. Carlson V, Delclo L, Fletcher GH. Distant metastases in squamous cell carcinoma of the uterine cervix. Radiology 1967;88:961-966.

7. Sotto LSJ, Graham JB, Pickren JW. Postmortem findings in cancer of the cervix. Am J Obstet Gynecol 1960;80:791-794.

8. Badib AO, Kurohara SS, Webster JH, et al. Metastasis to organs in carcinoma of the uterine cervix: Influence of treatment on incidence and distribution. Cancer 1968;21:434-439.

9. Lam KY, Tang V. Metastatic tumors to the spleen. Arch Pathol Lab Med 2000;124:526-530.

10. Chan YM, Ng TY, Ngan HY, et al. Monitoring of serum squamous cell carcinoma antigen levels in invasive cervical cancer: Is it cost effective? Gynecol Oncol 2001;84:7-11.

RELATED ARTICLE: Key Points

* Most commonly, metastases to the spleen are associated with widespread tumor dissemination throughout the abdominal cavity and/or other organs.

* Isolated solitary metastases in the spleen are rare, especially in recurrent disease.

* Posttreatment squamous cell carcinoma antigen monitoring is predictive of early detection of recurrence before the appearance of clinical symptoms.

* Splenectomy with postoperative chemotherapy was proposed because of the high risk of other microscopic foci of distant disease.

Leou Chuan Pang, MD

From the Department of Pathology, Chang-Gung Hospital and Chang-Gung University School of Medicine, Linkou, Tao Yuan, Taiwan.

Reprint requests to Leou Chuan Pang, MD, Department of Pathology, Chang-Gung Hospital and Chang-Gung University School of Medicine, Linkou, Tao Yuan, Taiwan. Email: [e-mail]