Abstract
Metastatic carcinoma of the spleen (MCS) is a rare condition which is frequency misdiagnosed. Research progress on the prevalence, clinicopathological features and diagnosis of MCS from the Chinese and English medical literature was reviewed to increase understanding of all aspects related to MCS. It is hoped that a better comprehension of MCS will increase the diagnotic level and the rate of MCS detection.
keywords
Metastatic carcinoma of the spleen (MCS) is considered to be rare, with case reports only occasionally seen in the Chinese and English medical literature. Extensive studies of the clinicopathologic features of MCS have seldom been conducted. It has been reported that its rate of misdiagnosis is high.[1] To enhance the understanding of the prevalence, clinicopathological features and means to diagnose MCS, research progress on MCS from the Chinese and English medical literature was reviewed to increase awareness of MCS and improve diagnostic methods and detection of this condition.
Prevalence of MCS
Splenic metastases are a clinical rarity compared to those seen in autopsies. The spleen is involved in metastatic malignancy in 6-13% of autopsies. Traditionally splenic metastases have been thought to occur late in a course of widely disseminated cancer, with the incidence of splenic involvement increasing up to 50% of cases where four or more solid organs are simultaneously involved. The improvement of imaging techniques and the advent of extensive use of imaging modalities, such as CT scans and magnetic resonance imaging (MRI) in cancer patient follow-up, have led to the identification of an increasing number of splenic metastases from different types of solid tumors. Thus our traditional ideas have been challenged.[2-4] A review of the Chinese medical literature regarding MCS (not including metastatic sarcoma of the spleen) between 1949 and 2004, resulted in a total of 98 cases (named “Chinese series”) with complete clinicopathological data (all almost were individual case reports). The age of the 98 patients (49 of each gender) ranged from 20-82 years (mean 52.7 years). The patients aging 31~70 years comprised 88.8% of the total. The mean age of the males was younger than females (49.4 vs. 54 years). The onset peak age of the males (31~70 years accounting for 87.8%) was younger than females (41~70 years accounting for 79.6%), a difference of approximately 10 years. Lam and Tang P1 in Hong Kong reported that the ratio of males to females was 1.7:1, and the age of the patients ranged from 11 ~ 85 years (mean 60 years). The patients of 70-80 years comprised 67%. The detection rate of MCS at autopsy and study of splenectomy specimens was 0.6% and 1.1% respectively. However, the reported rates in the Chinese medical literature were in 6.5% and 1.3%, respectively.[1,5]
Most of the MCS reported in the English literature also have been individual case reports resulting in more females than males. The age of the patients ranged from 11~84 years and most of these patients were 50~70 years old.[2,6] Splenic metastases ranked 10th among the 44 metastatic sites described in the literature. [4,7] Autopsy studies from the English literature showed a MCS detection rate to be 2.3~13%.[2,4,6] In cases of epithelial ovarian cancer, it may reach 19-52%.[8] Studies of splenectomy specimens showed it to be less, namely 5% to 7.4% (31/417 cases).[9,10]
Explanations proposed for the clinical relative paucity of splenic metastases have included: anatomically, the sharp angle where the splenic artery branches from the celiac artery; the scarcity of afferent lymphatic vessels may limit tumor metastasis; the rythemic contraction and the antitumor activity of the spleen, e.g., the splenic factor (a humoral substance produced in the spleen), macrophages, which squeeze out a tumor embolus and prevent its lodging and growing in the spleen.[1,4,11] However, there are authors who think that the low detection rate may involve some other rational causes. First, splenic biopsies performed at surgery in the past have been relatively rare. Even when splenectomy specimens were taken, the pathological examinations were not always carefully performed. Second, it is possible that MCSs were missed at diagnosis because of careless gross inspection of the splenic lesions by pathologists and of insufficient numbers of histological blocks prepared from the splenectomy specimens.[1]
Pathological Features
Size and distribution of MCS foci
In combined operative and imaging findings, 89 (90.8% ) of 98 patients in the Chinese series were found to have a MCS focus. Among 80 (81.6%) patients who had a reliable clinical record, the maximal diameter of their focus was from 0.8 cm to 20 cm with a mean of 6.7 cm greater than the 1.4 cm reported by Lam and Tang.[3] Most of the foci were involved in the upper pole, under pole or hilus of the spleen, and a few patients showed a complex involvement of the upper pole, the hilus and the capsule of the spleen or the under pole, the hilus and the capsule of the spleen.[1] The mean weight of the spleens with metastases was 143-178 g, so splenomegaly generally not to occur.[3,5] Paolini et al.[12] reported the a case of splenomegaly in which the initial manifestation was due to splenic metastasis from thyroid follicular adenocarcinoma. Occasionally, the spleen due to splenic metastases may weigh up to 1230 g (from endometrioid carcinoma of the ovary)[13] or 1250 g (from squamous cell carcinoma of the lung).[14]
Macroscopic typing
Macroscopical findings of MCS foci may present as mono-nodule, multi-nodule, diffuse infiltration and cysts.[3,12] The gross lesions of 21 MCS reviewed by Smart et al.[2] showed there were 5 cases for each of the mono-nodule, the multi-nodule and diffuse types, and no known pattern for 6 cases. Among the 74 cases reported by Lam and Tang,[3] 31 cases were mononodule type, 30 were multi-nodule, 5 diffuse and 8 cases predominately involved the splenic capsule. In the Chinese series 48 cases were mono-nodule, 36 multi-nodule, 3 diffuse, 2 predominately involved the splenic capsule, and for 9 case records were unknown. Liu et al.[5] had classified MCS into 4 types including nodular, diffuse, miliary and capsule. According to this classification, the nodular type was the most common (accounting for 85.7%) but the diffuse and the capsular types were seldom seen in the Chinese series. However, there were no miliary-type lesions in the Chinese series cases or in cases reported by Lam and Tang,[3] indicating that this type of lesion is uncommon.[1]
Histopathological typing
Almost all common tumors have been reported at some time to give rise to splenic metastases. The tumors that most commonly metastasized to the spleen were melanoma (34%), breast (12%), ovary (12%) and lung (9%) carcinoma. The less common tumors were choriocarcinoma, esophageal and endometrial.2,4,6] Occasinally, splenic metastases came from parotid, [11] bladder,[4] prostate[7] or testis carcinoma,[11] pseudomyxoma peritonei [15] or a ovarian granulosa cell tumor.1[16 Among the Chinese cases, the most common source of metastases to the spleen were from ovarian adenocarcinoma (17.4%), liver (15.3%), colon (15.3%), lung (10.2%), pancreas (10.2%) and stomach (8.2%) carcinoma followed by esophageal, choriocarcinoma (each 4.1%), papillary adenocarcinoma of the thyroid and adenocarcinoma of the small intestine (each 2%). The remaining (11.2%) less common sources came from small cell carcinoma of the lung, clear cell carcinoma of the lung, retropereitoneal chemodectoma, neuroendocrine carcinoma of the thymus, malignant islet cell adenoma, adenocarcinoma of the common bile duct, renal cell carcinoma, transitional cell carcinoma of the left renal pelvis, transitional cell carcinoma of the ovary, dysgerminoma of the ovary, and one case of an adenocarcinoma of an unclear origin. The histologic types of splenic metastases ranking first to sixth reported by Lam and Tang [3] and other internal literature were mainly identical with cases of the Chinese series with only slight changes in sequence.[17-18] In the Chinese series 79.6% (78/98 ) were adenocarcinoma, somewhat higher than the 70% (14/20 cases) and 62.1% reported by Liu et al.[5] and Lam and Tangl, [3] respectively. But only 13.3% (13 cases) were squamous cell carcinoma, lower than the 20% (4/20 cases) reported by Liu et al.,[5] compared to 12.6% noted by Lam and Tang.[3] In contrast, 10 of 12 cases reported by Chen et al.[19] were adenomas. These data indicate that the origin of the primary carcinoma in every series of patients is different.[1]
Route of metastasis
Splenic metastases are known to be more common from tumors with a strong propensity to develop hematogenous spread. Autopsy studies have shown that widespread carcinomatosis is present in more than 50% of the patients. Therefore, most splenic metastases are generally known to be hematogenous.[3,4,7] The data from the Chinese series showed MCS with simultaneous wide spread metastases to other locations to be 54.8% (53 cases). In addition, 39.8% had multinodular and diffused type foci in the spleen, supporting the concept that the route of MCS spreading is chiefly hematogenous. However, it was found that 20 cases (20.4%) also had isolated foci in the spleen of the Chinese patients, 2 patients had tumescent para-aortic lymph nodes, 4 cases showed tumefaction of lymph nodes in the splenic hilus of which there were lymph nodes metastases in 2 cases, one case had external and common iliac lymph nodes metastases all of which indicated that MCS may also metastasize by a lymphatic route.[5]
Clinical Features
Primary sources of MCS
Among MCS from the Chinese series patients, 76.6% of the primary tumors chiefly originated from the following carcinomas: ovarian, hepatocellular, colonic, lung, pancreatic and gastric followed by esophageal and choriocarcinoma (8.2%).These results differ considerably from the reports in which lung and mammary carcinoma comprised 30-67%, followed by colonic and ovarian carcinoma and melanoma.[2,4,14,20] The findings also differed from studies by Liu et al.[5] and Lam and Tang [3] in Hong Kong, who reported that the predominant carcinomas were ovarian, lung, nesopharyngeal, gastrointestinal, pancreatic and hepatocellular. Tatsuta et al.[11] indicated that 50 cases of MCS have been reported in the past 10 years in Japan. The primary tumors (80%) chiefly originated from colonic, gastric and ovarian carcinomas. These studies indicate that there is a difference in the prevalence, incidence and detection rate of cancers in various countries and areas.[1]
Time of detected MCS
Three characteristics of the Chinese series patients were the following: (1) Thirty-five cases (35.7%) were detected at the same time as the primary carcinoma. However, that was the situation in only 1 of 87 cases reported by Lam and Tang. [3] (2) Forty-seven cases (48%) were detected only after a latent period following confirmed diagnosis of the primary carcinoma (the longest was 24 years [21]). The latent period averaged 2.6 years, an obviously longer period than the mean of 6.7 months (the longest was 2 years) reported by Lam and Tang [3] and was in disagreement with the mean of 4.7 years (the longest was 7.3 years ) published by Gemingnani et al.[22] Chew et al.[16] reported 1 case with splenic, omental and pelvic metastasis of a granulosa cell tumor of the ovary 29 years after curative resection and 1 case of solitary splenic metastasis of a carcinoid tumor of the lung was found 8 years postoperatively.[23] A case of solitary splenic metastasis from a retropereitoneal chemodectoma was found 8 years postoperatively in China.[24] In the Chinese series patients there were 5 with a longer latent period including 6.4 years (ovarian adenocarcinoma) in 1 case, 7 years (1 antral gastric carcinoma and 1 ovarian serous cystadenocarcinoma) in 2 cases, 9 years (transitional cell carcinoma of the renal pelvis) in 1 case and 13 years (mucinous adenocarcinoma of the ovary) in 1 case. (3) Six MCS cases were detected prior to confirmed diagnosis of the primary carcinoma. The time periods were 1 month (1 papillary adenoma of the thyroid, 1 squamous cell carcinoma of the lung and 1 adenocarcinoma of the small intestine), 7 months (well-differentiated adenocarcinoma in the fundus of the stomach), 1 year (ovarian adenocarcinoma) and 3 years (adenocarcinoma of the splenic flexure of the colon). These cases are quite rare with only several having been reported in the literature to our knowledge.[6]
Symptoms and signs
Among MCS from the Chinese series patients, 65 (66.3% ) presented symptoms of tenderness and obscured or pain with bloating in the left upper quadrant of the abdomen. Sixty-six cases (67.3%) had a palpable masses in the left upper quadrant of the abdomen and splenomegaly to varing degrees. There were 78 cases (79.6%) with a splenic mass in varing sizes found during operation. In addition, a few patients displayed emaciation, anaemia, fever, nausea and vomiting. These results are different from those in the English literature in which MCS is infrequently associated with clinical symptoms and rarely with splenomegaly. [3,6,25] Because primary malignant tumors in the spleen are rare, we think the above-mentioned clinical symptoms and signs of MCS to be relatively specific and indicate a clinical diagnosis.[1]
Rare clinical manifestation of MCS
Rare clinical manifestations of MCS patients from the Chinese series were as follows:
Spontaneous rupture of the spleen secondary to MCS occured in 5 patients. Their primary carcinoma originated from adenocarcinoma of the splenic flexure of the colon in 2 cases, well-differentiated adenocarcinoma in the fundus of the stomach and serious cystadenocarcinoma of ovary and choriocarcinoma in 1 case, each. Spontaneous ruptures of MCS (except hematologic malignancies) were very rare.[9] Of the 87 MCS reported by Lam and Tang,[3] it occurred in only 2 cases. Spontaneous rupture of the spleen occurred up to 2004 in fewer than 40 cases reported in the English literature. Primary tumors that have resulted most commonly in splenic ruptures are pancreatic carcinoma, choriocarcinoma, melanoma and lung carcinoma, followed by carcinoma of the stomach and bladder. Other types are very rare. However, no reports of spontaneous splenic rupture secondary to metastatic adenocarcinoma of the colon or serous cystadenocarcinoma of the ovary have been found in the literature.[2,9]
MCS complicated by splenic abscess appeared in 5 patients in the Chinese series. Clinically, they presented with symptoms of constant fever etc. It is quite rare that 3 of these 5 patients were admitted to the hospital for spontaneous perforation of splenic abscess secondry to MCS.
Solitary MCS were observed in 15 cases. Primary tumors originated respectively from ovarian adenocarcinoma (3 serous cystadenocarcinoma, 1 mucinous cystadenocarcinoma and 1 poorly-differentiated adenocarcinoma) in 5 cases, colon-rectal adenocarcinoma in 4 cases and pulmonary carcinoma (1 squamous cell carcinoma and 1 adenocarcinoma) in 2 cases. The others (poorly-differentiated squamous cell carcinoma of the nasopharynx, small hepatocellular carcinoma, small intestinal mucinous adenocarcinoma, and retroperitoneal chemodectoma in 1 case, respectively) constituted 5 cases. Up to 2004 approximately 40 cases of solitary MCS had been reported in the English literature.[3,10] Among those tumors, ovarian adenocarcinomas were more frequent.[8,21,26] Up to that time only 8 cases of solitary MCS from colonic and lung carcinoma had been reported in the English literature.[10,27] To our knowledge there have been no reports of solitary MCS from small intestinal mucinous carcinoma.
The splenic metastases of the 18 patients came from rare primary carcinoma. The tumors included 2 cases of poorly-differentiated squamous cell carcinoma of the nasopharynx, 2 cases of thyroid carcinoma and one case of each of the following: esophageal carcinoma, clear cell lung carcinoma and small cell lung carcinoma, adenocarcinoma of the common bile duct, mucinous adenocarcinoma of the small intestine, renal cell carcinoma, transitional cell carcinoma of the left renal pelvis, poorly-differentiated squamous cell carcinoma of the cervix, poorly-differentiated transitional cell of the ovary, dysgerminoma of the ovary, endometrioid carcinoma of the ovary, neuroendocrine carcinoma of the thymus, malignant islet cell adenoma, and retropereitoneal chemodectoma. Among these tumors, thyroid, nasopharyngeal, esophageal, renal cell carcinomas (until 2001 only 4 cases had been reported in the English literature), cervical, endometrial carcinoma had been reported in the literature.[3,4,11,12,20,28-30] To our knowledge no other types of carcinoma have been reported. Some types of carcinomas in themselves are rare and seldom metastasize to the spleen as far as we know.
Small hepatocellular carcinoma with splenic metastasis occurred in 3 male patients. They underwent B-mode ultrasonography and CT examinations before operation. One of the patients had not been diagnosed with a carcinomous focus in the liver. The other 2 cases were known to have a hepatic carcinomous foci (only 2 cm and 2.5 cm in diameter).
However, a huge MCS focus and single or multiple MCS nodes occurred between 1 and 2 months in the 3 patients. Although a few cases of hepatocellular carcinoma with splenic metastasis had been reported, neither of these cases was small hepatocellular carcinoma.[31,32]
Clinical diagnosis
Although most patients in the Chinese series presented with evident symptoms and signs and related imaging features, only 7 (28%) of the 25 cases who showed a clinical diagnosis record were diagnosed with MCS. The remaining 18 cases (72%) were all misdiagnosed. The causes for misdiagnosis are as follows: (1) Misdiagnosis are unavoidable owing to the rarity of MCS, the insufficient understanding of clinicans concerning the clinicopathologic features of MCS and lack of their clinical experience. (2) Comprehensive analysis and the relationship of the clinical anamnesis of the primary carcinoma to imaging findings of the MCS were insufficient) Complicated pathologic changes and clinical manifestations are difficult to grasp. Due to the concomitant primary carcinoma and MCS, clinicians are frequently focused on the symptoms and signs of the primary carcinoma and therefore neglect the clinical manifestations of MCS.[1]
On the basis of clinicopathologic findings and misdiagnosed causes of the Chinese series cases, the author feels that the following matters should be emphasized with regard to diagnosis of MCS. (1) The symptoms and signs should be grasped with relative specificity. In the Chinese series, the majority of patients had continuous or repeated vague pains or gas pains in the left upper quadrant of the abdomen with a palpable mass or splenomegaly. Although these symptoms are not in accordance with reports concerning MCS in the literature, the author considers these symptoms and signs to be relatively specific and to be important evidence to clinically diagnose MCS.[1,3,6,25] (2) Imaging examinations (B-mode ultrasonography and CT) should be utilized fully to aid in clinical diagnosis. (3) Importance must be placed on the comprehensive analysis with regard to the carcinomatous history and clinical symptoms and signs and imaging findings and to find a correlation of the 3 aspects. This will enable diagnosis of MCS after confirmed diagnosis of the primary carcinoma. There are more complicated pathologic changes and clinic presentations for those MCS which are detected simultaneously with the primary carcinoma. The interrelation between the primary carcinomas and the MCS should be more seriously analyzed combined with the imaging findings to arrive at a correct diagnosis.[1,17-19] (4) The relationships between the clinical findings and pathology should be enhanced. Realizing that the detection rate of MCS is lower in China and that the real incidence may be higher, clinicans and pathologists should all enhance their awareness of MCS diagnosis. Surgeons should pay close attention to observe splenic lesions during operations. If some lesions are found, a biopsy should be performed. Routine histopathologic examination of all splenectomy specimens should be conducted. Pathologiests should also maintain close contact with the clinicans and careful macroscopic examinations of the splenic specimens from autopsies, biopsies or excision should be conducted. Patients with especially small metastatic foci in the spleen, which may be missed by imaging examination and have not obvious features by macroscopic examination should be considered carefully. Multiple tissue blocks from the entire spleen should be taken and careful microscopic examinations should be performed to increase the rate of MCS detection.[1,3]
- Received November 4, 2005.
- Accepted December 6, 2005.
- Copyright © 2006 by Tianjin Medical University Cancer Institute & Hospital and Springer
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