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The Korean Journal of 2008; 42: 317-22

Solitary Splenic Metastases from Uterine Cervical : Case Reports and Review of the Literature

Jo-Heon Kim1∙Yoo-Duk Choi1 Splenic from gynecologic tumors is extremely rare, especially in the absence of Jae-Hyuk Lee1,3∙Jong-Hee Nam1,3 apparent disease at other sites. We report two patients that underwent splenectomy for a Sang-Woo Juhng1,3∙Yang-Seok Koh2 solitary splenic metastasis from uterine cervical carcinoma. In case 1, a 54-year-old Chol-Kyoon Cho2∙Chan Choi1,3 with FIGO Stage IIb squamous carcinoma of the uterine treated with radiotherapy and developed a solitary splenic metastasis 10 months after initial treatment. Departments of 1Pathology and 2Surgery, In case 2, a 46-year-old woman with FIGO Stage IIb of the uterine cervix Chonnam National University Medical treated with radiotherapy and chemotherapy was found to have a solitary splenic metastasis School, Gwangju; 3Brain Korea 21 11 months after treatment. Thus all abdominal organs including the spleen must be evaluat- Project for Biomedical Human Resources ed for metastases during follow-up of gynecologic tumors. Center at Chonnam National University, Gwangju, Korea

Received : November 6, 2007 Accepted : July 31, 2008

Corresponding Author Chan Choi, M.D. Department of Pathology, Chonnam National University Medical School, 5 Hak-dong, Dong-gu, Gwangju 501-749, Korea Tel: 061-379-7071 Fax: 061-379-7079 E-mail: [email protected] Key Words : Uterine cervix; Gynecologic tumors; Splenic metastasis

The spleen is an uncommon site for tumor metastases. Most year history of and intermittent lower abdom- splenic metastases are found at autopsy as a part of widespread dis- inal pain in May of 2005. An exophytic mass measuring 5 cm in ease. Based on large clinicopathologic studies, the breast, , maximum diameter, involving all four quadrants of the cervix colorectum, and are the most common primary sources for and extending to the right upper vaginal fornices was detected splenic metastases.1 Splenic metastases are often on . A cervical punch was performed since the spleen is an internal organ with a large functional reserve.1 and the pathologic examination showed a keratinizing squamous Even though the incidence of splenic metastasis from gyne- cell carcinoma (SCC) of the uterine cervix (Fig. 1A). Pelvic MRI cologic tumors has increased, only 46 solitary splenic metastases showed a 5×4×4 cm mass in the uterine cervix with parame- were reported in a review of the English and European medical trial invasion (Fig. 1B). The chest X-ray, abdominal sonogram, literature. We report two patients that underwent splenectomy and colonoscopy were normal, confirming a FIGO stage IIb lesion. for metastases of gynecologic cancer. The two patients had soli- The spleen was unremarkable on the abdominal sonogram. The tary splenic metastases from the uterine cervix. patient was treated with radiotherapy, including external beam irradiation and . External beam two-dimensional radiation consisted of pelvic irradiation to a total dose of 113.4 CASE REPORTS Gy in 63 fractions at 1.8 Gy per fraction five times a week using 10 MV photons. Intracavitary brachytherapy was performed with Case 1 two intracavitary applications of Ir192. The combined dose to the tumor was 160.2 Gy until September 2005. In addition, treat- A 54-year-old woman was admitted to the hospital with a 1- ment with was given intravenously in 6 courses as ch-

317 318 Jo-Heon Kim∙Yoo-Duk Choi∙Jae-Hyuk Lee, et al. emotherapy (349.1 mg total dose) until June 2005. In January mass was found in the medial portion of the spleen with suspi- 2006, the patient was again treated with radiotherapy due to the cious splenic capsular invasion (Fig. 1C). The histologic exami- left pelvic lymphadenopathy detected by pelvic MRI. External nation revealed metastatic SCC of the cervix with splenic cap- beam two-dimensional radiation consisted of pelvic irradiation sule invasion (Fig. 1D). The patient was given 6 courses of a to a total dose of 14.4 Gy in 8 fractions at 1.8 Gy per fraction five chemotherapy regimen containing and carboplatin times a week using 10 MV photons. Serial SCC measure- (1,554 mg and 3,050 mg total doses, respectively) until August ments were performed at 3-month intervals. 2006. In September 2007, the SCC antigen level was elevated The patient remained free of disease until March 2006. Recur- again, (1.6 ng/mL), and a CT and PET scan showed a 2.5 cm rence was initially suspected on the basis of an elevated SCC recurrent mass in the perirectal spaces and cul de sac. The antigen level (3.2 ng/mL; normal, <1.5 ng/mL). However, the patient was again treated with radiotherapy. External beam patient did not complain of abdominal discomfort and no abdomi- two-dimensional radiation consisted of pelvic irradiation to a nal mass was palpated on physical examination. To confirm the total dose of 50.8 Gy. Moreover, the patient was given three recurrence, a CT scan and whole body positron emission tomog- courses of a chemotherapy regimen containing and cis- raphy (PET) scan were performed and a 3 cm mass was noted platin (10.7 mg and 219.5 mg total doses, respectively) until in the spleen; there was no recurrent mass in the uterine cervix, December 2007. A last CT scan showed a markedly regressed , parametrium, or regional lymph nodes. In March 2006 mass in January 2008, and the patient is alive without further a laparoscopic splenectomy was performed. A 3 cm firm yellow evidence of disease 4 months after completion of therapy.

100 μm A B

C 100 μm D

Fig. 1. (A) The photomicrograph of the uterine cervix (case 1) shows . (B) Pelvic MRI shows diffuse wall thick- ening in the uterine cervix with heterogeneous enhancement. (C) The cut surface of the spleen shows a relatively well-defined solitary yellowish white mass with capsular invasion. (D) Metastatic squamous cell carcinoma is seen in the spleen. Residual splenic parenchy- ma is observed at the bottom. Solitary Splenic Metastases from Uterine Cervical Cancer 319

Case 2 radiation consisted of pelvic irradiation to a total dose of 54 Gy in 30 fractions at 1.8 Gy per fraction five times a week using A 46-year-old woman was admitted to the hospital in Octo- 10 MV photons. Intracavitary brachytherapy was performed ber 2005 with a 4-month history of vaginal bleeding and inter- with one intracavitary application of Ir192. The combined dose mittent lower abdominal discomfort. On physical examination, to the tumor was 86.5 Gy up until January 2006. Cisplatin an exophytic mass, 3 cm in maximum diameter involving all chemotherapy was given intravenously in 6 courses (398.4 mg four quadrants of the cervix and extending into the right vagi- total doses) until December 2005. nal fornices, was observed. A cervical punch biopsy was per- The patient remains free of disease. The patient did not com- formed and the histologic examination showed an endocervi- plain of any abdominal discomfort, and an abdominal mass was cal-type mucinous adenocarcinoma of the uterine cervix (Fig. not found on physical examination. To detect any tumor recur- 2A). The pelvic MRI showed a 2.7×2.1 cm mass in the uter- rence or metastases, follow-up abdominal and pelvic MRI was ine cervix with parametrial invasion (Fig. 2B). The chest and performed in February and September 2006. In September abdominal X-ray were normal, confirming a FIGO stage IIb 2006, a 1.4 cm cystic mass was detected in the spleen, but no lesion. The upper abdomen was not evaluated by any other diag- recurrence was detected in the uterine cervix, regional lymph nostic procedure at that time, except an abdominal X-ray. The nodes, or other organs. A laparoscopic splenectomy was per- patient was treated with radiotherapy, including external beam formed in September 2006. The spleen showed a 2.4 cm hard irradiation and brachytherapy. External beam two-dimensional yellow mass with cystic changes (Fig. 2C). The histologic exam-

100 μm A B

C 100 μm D

Fig. 2. (A) The photomicrograph of uterine cervix (case 2) shows endocervical type mucinous adenocarcinoma. (B) Pelvic MRI shows a heterogeneously enhancing mass in the uterine cervix. (C) The cut surface of the spleen shows a well-defined solitary yellowish white solid mass with focal cystic change. (D) Metastatic adenocarcinoma is seen in the spleen. 320 Jo-Heon Kim∙Yoo-Duk Choi∙Jae-Hyuk Lee, et al. ination revealed metastatic adenocarcinoma of the cervix (Fig. 6 courses of a chemotherapy regimen containing paclitaxel and 2D). A few days after , a necrotic friable lesion was iden- carboplatin (1,750 mg and 3,794 mg total doses, respectively) tified in the uterine cervix on physical examination; a punch until February 2007. In June 2007, persistent adenocarcinoma biopsy revealed remnant adenocarcinoma. The patient was given was detected in the cervical thin-prep cytology, and the chest

Table 1. Reported cases of gynecological carcinomas with solitary splenic metastasis

Primary therapy Time of Primary tumor site Type of tumor Age References of cancer recurrence (months) Uterine cervix Squmaous cell carcinoma 43 NA 60 NA Uterine cervix Squmaous cell carcinoma 28 ChT, RT 20 6 Uterine cervix Adenocarcinoma 47 Op, ChT 60 6 Uterine cervix Squmaous cell carcinoma 47 RT 48 4 Uterine cervix Squmaous cell carcinoma 45 Op, RT 36 6 Uterine cervix Squmaous cell carcinoma 45 Op, RT 60 2 Uterine cervix Squmaous cell carcinoma 54 ChT, RT 10 Current case 1 Uterine cervix Adenocarcinoma 46 ChT, RT 11 Current case 2 Endometrium Endometrioid adenocarcinoma 66 Op, RT 24 6 Endometrium Endometrioid adenocarcinoma 59 Op 11 6 Endometrium Endometrioid adenocarcinoma 72 Op, RT 35 7 Endometrium Endometrioid adenocarcinoma NA NA NA 6 Endometrium Endometrioid adenocarcinoma 47 Op, ChT, RT 72 5 Endometrium Endometrioid adenocarcinoma 58 NA 28 6 Endometrium Endometrioid adenocarcinoma 52 Op, RT 30 8 Endometrium Endometrioid adenocarcinoma 53 Op, ChT 120 9 Endometrium Endometrioid adenocarcinoma 62 Op, RT 18 10 Ovary Serous NA NA 60 6 Ovary 50 RT NA 5 Ovary Endometrioid adenocarcinoma 58 Op, RT 36 11 Ovary Serous cystadenocarcinoma 54 Op, ChT 12 5 Ovary Serous cystadenocarcinoma 65 Op 60 6 Ovary Endometrioid adenocarcinoma 76 ChT NA 5 Ovary Serous cystadenocarcinoma 49 Op, ChT 80 5 Ovary Serous cystadenocarcinoma 57 Op, ChT 24 5 Ovary Serous cystadenocarcinoma 59 Op, ChT 120 5 Ovary Serous cystadenocarcinoma 79 Op, ChT 18 5 Ovary Endometrioid adenocarcinoma NA NA NA 5 Ovary Serous cystadenocarcinoma 55 Op, ChT 27 6 Ovary Carcinoma 41 Op, ChT 36 12 Ovary Adenocarcinoma 56 Op, ChT 24 5 Ovary Serous cystadenocarcinoma 45 Op, ChT 48 13 Ovary Serous cystadenocarcinoma NA NA NA 6 Ovary Mucinous cystadenocarcinoma 29 Op 12 3 Ovary Clear cell carcinoma 47 NA NA 14 Ovary Serous cystadenocarcinoma 67 NA 66 14 Ovary Serous cystadenocarcinoma 67 Op, ChT 36 14 Ovary Serous cystadenocarcinoma 70 Op, ChT 180 14 Ovary Serous cystadenocarcinoma 53 Op, ChT 27 14 Ovary Serous cystadenocarcinoma 53 Op, ChT 81 14 Ovary Serous cystadenocarcinoma 59 Op, ChT 108 14 Ovary Carcinoma 58 Op, ChT 65 15 Ovary Carcinoma 60 Op, ChT 30 15 Ovary Carcinoma 59 Op, ChT 6 15 Ovary Carcinoma 59 Op, ChT 14 15 Ovary Carcinoma 59 Op, ChT 21 15 Ovary Carcinoma 58 Op, ChT 32 15 Fallopian tube Adenocarcinoma 68 Op, RT 61 16

NA, not available; Op, operation; ChT, chemotherapy; RT, . Solitary Splenic Metastases from Uterine Cervical Cancer 321

CT showed multiple metastatic nodules (largest size, 1.6 cm) astinal and supraclavicular lymph nodes, and the liver. Unusual in both . The patient was given 6 courses of a chemother- metastases have been reported in the skin and soft tissues, gall- apy regimen containing cisplatin and 5- (660 mg bladder, and pericardium.4 and 30,000 mg total doses, respectively) until December 2007. In cervical , the clinical history and physical examina- A last chest CT scan showed more aggravated masses in both tion, routine follow-up with radiologic imaging, or lungs in January 2008, and the persistent adenocarcinoma was vaginal cytologic studies are performed to detect any evidence detected in the cervical punch biopsy in March 2008. Further of tumor recurrence or metastases. Serial SCC antigen measure- chemotherapy is under consideration at this time. ments have been performed for monitoring the course of dis- ease, response to treatment, and detection of tumor recurrence. The most important use for SCC antigen in SCC of the cervix DISCUSSION is its ability to accurately predict recurrence before the appear- ance of clinical symptoms. Furthermore, highly sensitive imag- Spleen metastases from various are rare. In virtu- ing techniques, such as the CT scan, MRI, and PET scan specif- ally all of these instances, splenic involvement is accompanied ically detect and confirm disease recurrence.2 Even though the by widespread metastases. Clinically-apparent isolated metas- gynecologic tumors uncommonly metastasize to the spleen, all tases to the spleen are exceedingly rare.1 abdominal organs, including the spleen, must be evaluated for The spleen is considered an unfavorable environment for the metastases during follow-up. For cases with isolated parenchy- development of metastasis, although the reason for this is not mal splenic metastasis, a laparoscopic splenectomy may play an fully understood. It is generally accepted that there are three important role for a prolonged disease-free interval.5 possible routes for the spread of tumor to the spleen: by the splenic artery, by the splenic vein, and through the lymphatics.2 Explanations proposed for the relative paucity of splenic metas- REFERENCES tases have included the role of the splenic capsule as a physical barrier, the acute angle at the origin and the tortuosity of the 1. Lam KY, Tang V. Metastatic tumors to the spleen: a 25-year clinico- splenic artery, the lack of afferent lymphatics in the splenic pathologic study. Arch Pathol Lab Med 2000; 124: 526-30. parenchyma, the rhythmic contractile properties of the spleen, 2. Pang LC. Solitary recurrent metastasis of squamous cell carcinoma and the immune competence and possible antineoplastic nature of the uterine cervix in the spleen: case report. South Med J 2004; of the splenic tissue itself.3 97: 301-4. Currently, the literature contains only a few reports of splenic 3. 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