Context.—Splenic rupture secondary to solid malignancy is an infrequent complication that usually occurs late in the progression of a previously diagnosed cancer. In rare instances, splenic rupture precipitates the discovery of an unsuspected pancreatic carcinoma. We report 2 cases of adenocarcinoma of the pancreas in which the patients presented with splenic rupture.

Objectives.—To review the clinicopathologic features of splenic rupture due to pancreatic carcinoma and to increase awareness of malignancy as a possible etiology for atraumatic splenic rupture.

Design.—We reviewed the clinical and pathologic data from 2 patients. A literature search was conducted to identify previous reports of splenic rupture associated with pancreatic cancer. We summarized the characteristics of the earlier cases and compared them with those of our patients.

Results.—We found only 4 previous reports of splenic rupture preceding the diagnosis of pancreatic cancer. In 3 of these cases, the pancreatic carcinoma grossly invaded the spleen at the time of resection. In contrast, malignancy was not suspected as the etiology of the rupture in our patients until histologic examination of the resected spleen revealed carcinoma.

Conclusion.—Splenic rupture is an unusual presentation of cancer of the pancreas, and to our knowledge only 4 cases have been reported previously in the literature. Although an underlying malignancy is relatively rare, spleens resected for atraumatic rupture should be carefully examined for possible neoplastic etiologies.

Rupture of a diseased spleen in the absence of trauma can be defined as a pathologic rupture. Pathologic splenic ruptures are associated with a variety of conditions, including infections, congenital anomalies, metabolic disorders, degenerative conditions, and malignancies. Among these etiologies, infectious mononucleosis is the most common cause of pathologic splenic rupture in the Western world.1 Although neoplasms are less frequently implicated, hematologic malignancies are a well-known cause of rupture.1 In contrast, nonhematologic neoplasms are very rarely associated with splenic rupture, and fewer than 40 cases have been reported in the literature to date. The most common solid tumor metastases identified in ruptured spleens include choriocarcinomas (in women), melanomas, and lung carcinomas.2–4 

Carcinoma of the pancreas is generally associated with nonspecific symptoms that suggest a wide range of differential diagnoses. Initial symptoms may include dyspepsia, early satiety, and nausea. Classically, a patient presents late in the disease course with weight loss and obstructive jaundice. Other late symptoms include spasmodic epigastric pain relieved by positional changes, vomiting, and diarrhea.5 Tumors in the body or tail of the pancreas tend to present later than those in the head of the pancreas, and the patient may experience epigastric pain that radiates to the back. Splenic rupture is a very rare presenting sign of pancreatic carcinoma, and to our knowledge only 4 cases have been reported previously.6–9 Regardless of etiology, clinical signs of splenic rupture include pain, tenderness, and muscle guarding in the left upper quadrant of the abdomen, as well as shoulder pain, nausea, vomiting, dizziness, and syncope.1,10 

In the cases described in this article, the patients sought medical attention owing to symptoms caused by atraumatic splenic rupture. At splenectomy, each patient's pancreas appeared grossly normal, and cancer was not suspected until after microscopic examination of the resected spleen.

Case 1

A 57-year-old man presented to his primary care physician with a 1-week history of bandlike pain around his waist and in his right upper quadrant. The patient had no history of trauma and was previously in good health. A computed tomographic (CT) scan of the abdomen and pelvis showed a large, subcapsular, perisplenic fluid collection associated with the pancreatic tail (Figure 1). There was no evidence of pancreatitis. Additionally, there was splenic hilum collateral vasculature suggestive of thrombosis or stenosis of the splenic vein. On exploratory laparotomy, the spleen appeared macerated. It was difficult to remove owing to the encapsulated nature of the rupture with adhesions to multiple areas in the posterior left upper quadrant. As no splenic vein was observed in the hilum, it was presumed to be completely thrombosed. Owing to the microscopic findings of atypical glands in the spleen, the initial CT scans were re-evaluated, and a mass was identified in the pancreatic tail. Subsequently, the distal pancreas and part of the stomach were resected, and a biopsy was taken from the diaphragm.

Figure 1.

Computed tomographic scan of the abdomen with contrast demonstrates a large, low-density fluid collection (yellow arrow) that depresses the splenic parenchyma and is associated with the pancreatic tail. No definitive mass was identified in the pancreas prior to the splenectomy. Figure 2. Group of atypical glands within parenchyma of the ruptured spleen (hematoxylin-eosin, original magnification ×200). Figure 3. A, Moderately differentiated adenocarcinoma infiltrating through desmoplastic stroma into the peripancreatic soft tissue (hematoxylin-eosin, original magnification ×100). B, Dysplastic papillary mucinous epithelium lining the pancreatic duct (hematoxylin-eosin, original magnification ×200). Figure 4. Resected distal pancreas (green arrow) with area of gray-white induration (red arrow) and a 12.5 × 10.5 × 7.5-cm cyst. Figure 5. A, Papillary mucinous epithelium lining the cyst (hematoxylin-eosin stain, original magnification ×40). B, Invasive pancreatic carcinoma consisting of signet ring cells in a pool of mucin (hematoxylin-eosin, original magnification ×200). C, Carcinoma invading remnants of splenic parenchyma present in the distal pancreatectomy specimen (hematoxylin-eosin, original magnification ×200)

Figure 1.

Computed tomographic scan of the abdomen with contrast demonstrates a large, low-density fluid collection (yellow arrow) that depresses the splenic parenchyma and is associated with the pancreatic tail. No definitive mass was identified in the pancreas prior to the splenectomy. Figure 2. Group of atypical glands within parenchyma of the ruptured spleen (hematoxylin-eosin, original magnification ×200). Figure 3. A, Moderately differentiated adenocarcinoma infiltrating through desmoplastic stroma into the peripancreatic soft tissue (hematoxylin-eosin, original magnification ×100). B, Dysplastic papillary mucinous epithelium lining the pancreatic duct (hematoxylin-eosin, original magnification ×200). Figure 4. Resected distal pancreas (green arrow) with area of gray-white induration (red arrow) and a 12.5 × 10.5 × 7.5-cm cyst. Figure 5. A, Papillary mucinous epithelium lining the cyst (hematoxylin-eosin stain, original magnification ×40). B, Invasive pancreatic carcinoma consisting of signet ring cells in a pool of mucin (hematoxylin-eosin, original magnification ×200). C, Carcinoma invading remnants of splenic parenchyma present in the distal pancreatectomy specimen (hematoxylin-eosin, original magnification ×200)

Close modal

After the distal pancreatectomy for pancreatic adenocarcinoma, the patient received radiation and radiosensitizing chemotherapy treatments. Almost 3 months later, he was readmitted with a small bowel obstruction. Adhesions and peritoneal and mesenteric metastases were resected, and a small bowel bypass was performed. With continued chemotherapy, his serum CA 19-9 levels showed a decreasing trend. Eleven months after the pancreatectomy, the patient developed another malignant bowel obstruction. Exploratory laparotomy revealed unresectable metastatic involvement of the abdominal wall. In the most recent medical record available to us, the patient was terminally hospitalized with metastatic cancer.

Case 2

A 49-year-old woman was transferred from an outside hospital with a 4-month history of left upper quadrant abdominal pain. Although the low-grade and nearly constant pain had acutely worsened 3 days earlier, she recalled no episode of trauma. Her past medical history was remarkable for obesity, diabetes mellitus, smoking, and a cholecystectomy. An abdominal CT scan performed at the referring hospital had revealed a subcapsular hematoma of the spleen. On admission, the patient was afebrile with normal vital signs. She had left upper quadrant abdominal tenderness, but no diffuse peritoneal signs. An exploratory laparotomy and splenectomy were performed.

Pathologic examination of the spleen revealed a cyst lined by atypical mucinous epithelium. A repeat abdominal CT scan showed no evidence of a pancreatic mass or dilatation of the pancreatic or common bile duct. However, the postsurgical splenic bed contained an abscess that was subsequently drained. Postoperatively, the patient's serum level of the cancer antigen CA 19-9 was 10 U/mL (10 kU/L), or within the normal range. Owing to her poor medical condition, further workup for the etiology of the splenic cyst was not performed at this time.

Eleven months later, the patient presented with increasing abdominal pain and an elevated white blood cell count. An abdominal CT scan demonstrated a fluid collection directly adjacent to the tail of the pancreas. The aspirated fluid had no microbial growth or malignant cells, but contained 5756 U/L (95.95 nkat/ L) of amylase. Her serum CA 19-9 level was moderately elevated at 116 U/mL (SI units, 116 kU/L; normal range, 0–37 U/mL [0– 37 kU/L]), while the carcinoembryonic antigen level was normal. She also had multiple kidney stones; the largest stone obstructed the left ureter and may have caused the abdominal pain. The abdominal fluid collection was thought to represent a pancreatic pseudocyst. It resolved following drainage.

After 17 months (2.5 years after the splenic rupture), the patient developed another cyst near the pancreas. In light of the cyst recurrence and the glandular tumor in the spleen, a distal pancreatectomy was performed. In addition to the pancreatic tail, the surgeons removed the adjacent cyst and adherent portions of diaphragm and stomach. Histologic examination revealed an invasive mucinous cystadenocarcinoma of the pancreas.

Two months after the distal pancreatectomy, the patient was hospitalized with an intra-abdominal abscess in the left upper quadrant. She was treated with intravenous antibiotics, and the abscess was drained. The patient has been free of recurrences for more than a year.

Case 1

Grossly, the spleen weighed 305 g and measured 14.0 × 11.0 × 5.0 cm. There was a large subcapsular space containing necrotic tissue and clotted blood. Sections through the splenic parenchyma revealed multiple tan-yellow areas on the capsular surface adjacent to the subcapsular space. Microscopically, these areas showed focal groups of atypical glands with hyperchromatic nuclei and increased mitotic activity, consistent with an adenocarcinoma (Figure 2). The cells showed positive immunostaining for cytokeratin 7 and negative staining for cytokeratin 20 and prostate-specific antigen. The hematoxylin-eosin and immunohistochemical findings were not specific, but were consistent with a pancreatic primary.

In the distal pancreatectomy specimen, the segment of pancreas measured 11.5 × 6.0 × 3.5 cm and showed a dilated duct. Contiguous with the duct was a cystic structure that measured 3.0 cm in greatest dimension. The cyst wall was indurated and light tan, and the lining was shiny, light tan, and slightly wrinkled. A 4.0 × 2.2 × 2.0-cm solid mass was present in the cyst wall. Microscopic sections showed a moderately differentiated ductal adenocarcinoma extending into the peripancreatic soft tissue (Figure 3, A). The tumor appeared to be arising in an intraductal papillary mucinous tumor (Figure 3, B). There was no perineural or lymphovascular invasion, and 7 peripancreatic lymph nodes were negative for metastasis. Fibrous serosal adhesions to the stomach and biopsies from the diaphragm contained adenocarcinoma.

Case 2

The spleen weighed 340 g and measured 14.2 × 11.5 × 4.7 cm. There was extensive capsular disruption over the lateral surface with adherent blood clots and an associated subcapsular hemorrhage. An additional area of hemorrhage was observed adjacent to parenchymal blood vessels near the center of the spleen. One pole of the spleen contained an empty 2.2 × 1.8 × 0.6-cm cystic cavity. Microscopic examination revealed a cystic mucinous tumor within fibrous splenic parenchyma. The cystic lesion was partially lined by atypical epithelial cells and papillary mucinous epithelial fragments. No ovarian-type stroma was identified. Intravascular thrombi and associated hemorrhage were also present.

The resected segment of distal pancreas measured 10.0 × 9.0 × 3.5 cm and was attached to a 12.5 × 10.5 × 7.5-cm cyst that was not in continuity with the pancreatic ductal system (Figure 4). The cyst had a dark pink, smooth, dull surface. On section, it was unilocular and lined by a dark pink-gray, friable material with yellow papillary excrescences. Between the cyst and the pancreas was a 5.5 × 3.0-cm, gray-white indurated area with fragments of tissue resembling spleen. Histologic examination showed an invasive moderately to poorly differentiated mucinous cystadenocarcinoma of the pancreas. The cystic area of the tumor was partially lined by dysplastic columnar mucinous epithelium (Figure 5, A). There was invasive cancer in the cyst wall and the adjacent solid areas. The cyst wall showed hyalinization without definite ovarian-type stroma. Some areas of the tumor consisted of glands in a desmoplastic stroma, while other areas showed glands in mucin pools with some signet ring cells (Figure 5, B). Ducts in the adjacent pancreas had foci of pancreatic intraepithelial neoplasia/lesions IA and IB. The tumor extended into the peripancreatic soft tissue, was present throughout the stomach wall, and involved remnants of spleen (Figure 5, C). Additionally, there was perineural and lymphovascular invasion with 12 of 18 lymph nodes positive for metastatic adenocarcinoma.

Both of our cases represent an unusual presentation of pancreatic cancer. To our knowledge, only 4 similar instances have been reported previously in the English language since 1965 (Table). Most recently, Yettimis et al6 described a 61-year-old man who presented with a 10-day history of mild left abdominal pain that had worsened acutely. The patient had tenderness and guarding in his left abdomen. He also reported a 5.44-kg weight loss over 4 months and 15 years of alcohol abuse. A CT scan revealed free abdominal fluid and a tumor involving the tail of the pancreas and the splenic hilum. Grossly, the spleen was mostly decapsulated, and microscopic examination showed a pancreatic ductal adenocarcinoma. The tumor also invaded and obstructed the major vein of the spleen, presumably causing the rupture.

Cases of Pancreatic Cancer Presenting as Splenic Rupture

Cases of Pancreatic Cancer Presenting as Splenic Rupture
Cases of Pancreatic Cancer Presenting as Splenic Rupture

Chung et al8 described a similar case involving a 53-year-old man. The patient was admitted with a fever of 72 hours' duration and was found to have a left subcostal mass. Ultrasound and CT imaging of the mass were suggestive of a left subphrenic abscess. When the patient began bleeding from a gastric ulcer and exhibiting signs of hypovolemic shock, an exploratory laparotomy was performed. In addition to the bleeding ulcer, the surgeons found a perisplenic hematoma and a pancreatic tail carcinoma invading the splenic hilum.

The only prior report of splenic rupture in a woman with pancreatic cancer was published by Patrinou et al.7 The 69-year-old woman had pain in the left hypochondrium that radiated to her shoulder. At admission, she was afebrile and had a tender mass below the left costal margin. Abdominal CT showed a subcapsular splenic hematoma and a large, irregular, cystic lesion at the splenic hilum. Initially she was treated conservatively; however, an urgent exploratory laparotomy was performed after she exhibited signs of shock. The surgeons removed a large mucinous cystadenocarcinoma that involved the pancreatic tail and was attached to the splenic hilum. Cystic tumor nodules replaced almost two thirds of the splenic parenchyma, and the splenic vein was obstructed.

Chirman9 reported a splenic rupture in a 51-year-old man who presented with a 1-week history of intermittent epigastric pain that also involved the left shoulder and back. The patient did not recall any abdominal trauma, but he reported consuming approximately 1 pint of whiskey per week. The resected spleen had a large tear in the posterior surface and microscopic hyalinization of trabecular arteries, but no other evidence of intrinsic or metastatic disease. Five months later, the man was readmitted with abdominal pain, nausea, and a 22.7-kg weight loss. Exploratory laparotomy revealed extensive carcinoma of the pancreas. This case represents the only instance in which the resected spleen did not show gross and/or microscopic evidence of pancreatic cancer at presentation.

Inadequate sampling likely explains the failure to detect carcinoma in the spleen. Alternatively, the presence of atrophic pancreatitis and the patient's history of alcohol consumption raise the possibility that chronic pancreatitis may have been responsible for the splenic rupture. Splenic complications of chronic pancreatitis are rare, but they can include intrasplenic pseudocyst, subcapsular hematoma, or splenic rupture. It has been demonstrated that splenic complications occur more frequently in those with pancreatic tail necrosis, distal pancreatic pseudocysts, and splenic vein occlusions.11 Therefore, it is possible that the splenic rupture in the case reported by Chirman9 was not due to the malignancy.

The most common pathogenic mechanisms underlying pancreatic carcinoma in the spleen include direct spread and metastasis. Unlike our cases, 3 of the 4 previously reported cases involved a pancreatic tail tumor that grossly invaded the spleen at the initial operation. Gross involvement of the spleen by pancreatic carcinoma was not evident at the time of splenectomy in our patients, raising the possibility of a metastatic origin. Splenic metastases are relatively rare, occurring in fewer than 10% of postmortem examinations and fewer than 5% of splenectomy specimens.4,12 Rupture due to splenic metastasis is even less common than rupture secondary to direct invasion by tumor. In a retrospective study by Lam and Tang,4 splenic metastases were usually asymptomatic and resulted in splenic rupture in fewer than 3% of cases, none of which were associated with pancreatic carcinoma. Whether it is due to tumor invasion or metastasis, when splenic rupture does occur it is often a harbinger of a more advanced cancer.

Despite the lack of obvious gross pancreatic carcinoma, our cases may represent direct splenic invasion of carcinoma rather than metastasis. In case 1, the surgeons documented that during the splenectomy, the ruptured spleen was difficult to remove because of extensive adhesions. It is likely the adhesions were related to direct spread of the cancer, although the pancreatic carcinoma was not identified during the initial operation. In fact, during the subsequent distal pancreatectomy, the adhesions were noted to contain adenocarcinoma. In case 2, the distal pancreatectomy was performed more than 2 years after the splenectomy. The cystic tumor in the spleen could have been a pancreatic tumor that extended directly into the spleen or a metastasis from an occult pancreatic cancer. In both cases, it is impossible to determine with certainty whether the pancreatic carcinoma metastasized or spread directly to the spleen at presentation.

Rarely, pancreatic carcinoma of the spleen arises in the presence of a grossly and histologically normal pancreas.13–15 It has been hypothesized that these carcinomas may arise in heterotopic pancreatic tissue within the spleen, a theory further supported by the demonstration of normal pancreatic tissue within the spleen. Heterotopic pancreas is more commonly reported in the gastrointestinal tract than in the spleen.14 Regardless of location, heterotopic pancreas can develop the same pathologic conditions that affect the pancreas itself. Interestingly, all of the cases suspected to arise in heterotopic pancreas were mucinous cystadenocarcinomas, which frequently presented as splenic cysts. Although both our case 2 and the case reported by Patrinou et al7 were mucinous cystadenocarcinomas, remnants of normal pancreatic tissue were not present within the resected spleens. Therefore, a pancreatic origin for the carcinoma is likely.

Many mechanisms of atraumatic splenic rupture have been postulated. Among those attributed to hematologic malignancies are distention secondary to infiltration of the splenic parenchyma and capsule, defects in coagulation, and splenic infarct with capsular hemorrhage.10 The role of solid malignancies in splenic rupture is even less well understood. Disruption of the splenic blood flow secondary to thrombosis could result in infarction, hemorrhage, and possibly rupture. Thrombophlebitis is frequently associated with pancreatic carcinoma and could presumably occur within the spleen. In case 1, the splenic vein was not observed in the hilum of the spleen and was presumed to be thrombosed, and the splenic vessels in case 2 contained microscopic thromboses. Similarly, obstruction of splenic vessels due to tumor infiltration was observed in 2 of the previously reported cases (Table). Cystic dilation could also distend the splenic capsule and cause rupture. In both our mucinous cystadenocarcinoma (case 2) and the case reported by Patrinou et al,7 the resected spleens contained cystic cavities or nodules.

In summary, our cases demonstrate splenic ruptures as a rare presentation of pancreatic carcinoma. Neither patient had gross evidence of pancreatic carcinoma at the time of initial surgery. In one case, the pancreatic cancer was identified immediately after pathologic examination of the resected spleen, while in the second case the pancreatic carcinoma was not recognized until 28 months after splenectomy. Although splenic rupture is a rare presenting sign of pancreatic carcinoma or other malignancies, careful pathologic examination and surgical exploration are recommended to identify possible neoplastic etiologies.

Debnath
,
D.
and
D.
Valerio
.
Atraumatic rupture of the spleen in adults.
J R Coll Surg Edinb
2002
.
47
:
437
445
.
Smart
,
P.
,
M.
Cullinan
, and
G.
Crosthwaite
.
Spontaneous splenic rupture secondary to metastatic gastric carcinoma: case report and review.
Aust N Z J Surg
2002
.
72
:
153
155
.
Hoar
,
F. J.
,
S. Y.
Chan
,
P. S.
Stonelake
,
R. W.
Wolverson
, and
D.
Bareford
.
Splenic rupture as a consequence of dual malignant pathology: a case report.
J Clin Pathol
2003
.
56
:
709
710
.
Lam
,
K. Y.
and
V.
Tang
.
Metastatic tumors to the spleen: a 25-year clinicopathologic study.
Arch Pathol Lab Med
2000
.
124
:
526
530
.
Barkin
,
J. S.
and
J. A.
Goldstein
.
Diagnostic approach to pancreatic cancer.
Gastroenterol Clin North Am
1999
.
28
:
709
722
.
xi
.
Yettimis
,
E.
,
V.
Trompetas
,
N.
Varsamidakis
,
N.
Courcoutsakis
,
V.
Polymeropoulos
, and
E.
Kalokairinos
.
Pathologic splenic rupture: an unusual presentation of pancreatic cancer.
Pancreas
2003
.
27
:
273
274
.
Patrinou
,
V.
,
G.
Skroubis
,
V.
Zolota
, and
C.
Vagianos
.
Unusual presentation of pancreatic mucinous cystadenocarcinoma by spontaneous splenic rupture.
Dig Surg
2000
.
17
:
645
647
.
Chung
,
S.
,
K.
Park
, and
A. K.
Li
.
A pancreatic tumour presenting as a ruptured spleen.
HPB Surg
1989
.
1
:
161
163
.
Chirman
,
S. B.
Rupture of the normal spleen and cancer of the pancreas.
Calif Med
1965
.
102
:
227
230
.
Canady
,
M. R.
,
R. E.
Welling
, and
S. L.
Strobel
.
Splenic rupture in leukemia.
J Surg Oncol
1989
.
41
:
194
197
.
Malka
,
D.
,
P.
Hammel
, and
P.
Levy
.
et al
.
Splenic complications in chronic pancreatitis: prevalence and risk factors in a medical-surgical series of 500 patients.
Br J Surg
1998
.
85
:
1645
1649
.
Berge
,
T.
Splenic metastases: frequencies and patterns.
Acta Pathol Microbiol Scand [A]
1974
.
82
:
499
506
.
Zanetti
,
G.
,
L.
Riccioni
,
C.
Gallo
,
N.
Salfi
, and
G. N.
Martinelli
.
Splenic mucinous cystadenocarcinoma arising in heterotopic pancreatic tissue.
Tumori
1998
.
84
:
606
610
.
Nisar
,
P. J.
,
A. M.
Zaitoun
,
D. N.
Lobo
, and
B. J.
Rowlands
.
Heterotopic pancreas in the spleen: malignant degeneration to mucinous cystadenocarcinoma.
Eur J Gastroenterol Hepatol
2002
.
14
:
793
796
.
Hirota
,
M.
,
N.
Hayashi
, and
T.
Tomioka
.
et al
.
Mucinous cystadenocarcinoma of the spleen presenting a point mutation of the Kirsten-ras oncogene at codon 12.
Dig Dis Sci
1999
.
44
:
768
774
.

The authors have no relevant financial interest in the products or companies described in this article.

Author notes

Reprints: Wendy L. Frankel, MD, Department of Pathology, The Ohio State University Medical Center, E401 Doan Hall, 410 W 10th Ave, Columbus, OH 43210-1228 ([email protected])