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Spindle cell stromal tumor of the pancreas: Treatment by pancreatoduodenectomy
Brief clinical
reports
Spindle cell stromal tumor pancreas: Treatment by pancreatoduodenectomy Clarence
From Duke
H. Owen,
MD,
John
the Division of Hepatobiliary Universit~l AIedical Center;
F. Madden,
Swgery Durham,
MD,
PhD,
and Liver N C.
OF THE p.wcmks is rare, and criteria for classification and prognosis are less firmly established than for similar tumors at other sites in the gastrointestinal tract. Sarcomas comprise less than 0.1% of pancreatic malignancies overall, and in a large review of 5075 histologically confirmed primary pancreatic malignancies collected between 1955 and 1969, only five sarcomas were f0und.l A few case reports concern distinctive sarcoma subtypes such as liposarcoma,’ rhabdomyosarcoma, or osteogenic sarcoma,3 but the largest group of cases in both the older and recent literature appear to be sarcomas with a spindle cell structure. These are most often classified as leiomyosarcoma, although definitive evidence of smooth muscle differentiation has not always been provided in these reports. We recently encountered an unusual case of a primary spindle cell neoplasm that appeared to arise primarily in the head of the pancreas. Despite the large size of the tumor at presentation and histologic features compatible with malignancy, the history suggested an indolent rate of growth. The tumor was completely resected by means of pancreatoduodenectomy and the patient remained free of disease 2 years after operation. A review of our surgical records located a second case in which a spindle cell stromal tumor presenting clinically as a pancreatic head mass and pathologically S.MCOM.A
;2ccepted
for publication
1997;122:10511. Q 1997 by Mosby-l’ear
0039-6060,/97,:$5.00+0
Trans$a~~tati.o~~,
Clavien,
Departments
MD,
of Sulgry
PhD,
Dzu%zm,
AT C.
and PathoLog?,
involving the pancreatic head was similarly resected with apparent cure. Here we report both cases and review the literature regarding presentation, classification, therapy, and prognosis of primary spindle cell neoplasms of the pancreas. METHODS Surgical pathology reports of 337 surgical resections and open and percutaneous needle biopsies of pancreatic masses, representing all such material examined pathologically at Duke University Medical Center from 1979 until 1995, were reviewed (Table I). In seven cases (2.1%) the pathologic diagnosis was sarcoma involving the pancreas. Histologic material and patient records were reviewed. Two patients (0.6% of all pancreas specimens) had a spindle cell neoplasm that presented clini-
Sept. 9, 1996.
Reprint requests: Pierre A. Clavien, MD, PbD, Associate Chief, Hepato-Bilk-y Surgery & Liver Transplantation, Duke University Medical Center. Durham, NC 27710. Surgery Copyighr
and Pierre-Alain
of the
Book,
11/'57/79769
Inc.
Professor, Box 3247, Fig. 1. Axial CT images mass arising from head periaortic Iymphadenopathy mesenteric artery.
demonstrate large, hypervascular of pancreas with no suggestion of or encasement of superior
SURGERY
105
106
SUTgXT~ July 1997
Owen, Madden, Clavien
Fig. 2. Tumor histology is characterized by interlacing fascicles of spindle cells with scattered, dilated vascular spaces (case 1) (A, hematoxylin-eosin stain; original magni!Zcation x100). High power view shows fairly uniform nuclear structure with occasional mitoses (B, hematoxylineosin stain; original magnilication x400).
Table I. Pancreas neoplasms at Duke University Medical Center between 1979 and 1995”
Carcinoma Neuroendocrine neoplasm Ampullary carcinoma Cystic neoplasm Lymphoma Sarcoma Total “Derived from and incidental
No. of cases
Percent of total
229 32 28 25 15 2 331
69.2 9.7 8.5 7.6 4.5 0.6
total of 67‘2 specimens excluding pancreatitis benign pancrks biopsies (n = 62).
(n = 274)
tally as a pancreatic head massand are presented in detail below. In the remaining casesthe tumor arose clinically from nearby structures (malignant stromal tumor of the stomach, one case, and of the duodenum, three cases)and involved the pancreas secondarily or represented a metastasis from a remote site (malignant fibrous histiocytoma of the scapula, one case). In one additional case a highgrade sarcomatoid
malignancy
of the pancreatic
head
resembling malignant fibrous histiocytoma showed immunohistochemical reactivity for cytokeratin and wastherefore classifiedasprobable sarcomatoid carci-
surgery Volume
Owen, Madden, 122, Number
Clauien
107
1
Fig. 3. Tumor infiltrates between pancreatic acini (case 2) (A, hematoxylin-eosin stain; original magnification x170). High power shows pleomorphic spindle cells with fibrillar cytoplasm and blunt-ended nuclei, fairly uniform nuclear structure with occasional mitoses (B, hematoxylin-eosin stain; original magnification x520).
noma, even though
electron
microscopic
examination
failed to discloseevidence of epithelial derivation. CASE REPORTS Case 1. A 47-year-old white woman presented to her local physician with a palpable mass in the right upper quadrant. The patient reported a sense of fullness in the area for several years, but there were no other symptoms. Laboratory examination disclosed mild anemia (hemoglobin, 8.4 gm/dl) and liver dysfunction (aspartate aminotransferase, 115 units/l; alanine aminotransferase, 102 units/l; alkaline phosphatase, 140 units/L) without jaundice (total bilirubin, 0.3 mg/dl). An abdominal computed tomography (CT) scan
revealed a large, hypervascular mass in the right upper quadrant associated with the head of the pancreas and the right lobe of the liver and extending across the midline (Fig. I). An arteriogram showed the vascular supply horn the gastroduo denal and superior mesenteric arteries. At laparotomy an 11 x 10 x 9 cm, solid mass was found in the head of the pancreas displacing the surrounding duodenum, liver, stomach, and colon. Pancreatoduodenectomy was performed without preservation of the pylorus (Whipple operation). Blood transfusion was not required. The patient had an uneventful recovery and was discharged home on postoperative day 11. Gross examination of the resected specimen showed the mass distorting the head of the pancreas, encasing
108
Grgery July 1997
Owen, Madden, Clavien
Table II. Summary of 26 casesconsistent with diagnosis of primary spindle cell stromal tumor of the pancreas Clinical presenta.tion
Authm
Yea.r
Oesterlin and Blumenthal’
1935
57/F
Arel’ Brunschwigs
1949
1949
Feather and Kuhn5 Ross9 Judd and Hill” Berman and Levene’? Becker et al.” Brooke and Maxwell1s Neibling’” Chevrel’” Baylor and Berg’ Margules et a1.16
Operation
7
Laparotomy
48/M 37/M
Weight loss, painless jaundice Abdominal pain Abdominal pain
5 8
1951
29/M
Abdominal
6
1951 1954 1956
80/M 31/M 47/M
Palpable mass Gastrointestinal bleed Painless jaundice
5.5
Enucleation Subtotal distal pancreatopneumectomy Total pancreatectomy None Whipple Whipple
1965 1966
NR 44/M
NR 6
NR Whipple
1968
29iF
NR Abdominal pain, jaundice Palpable mass
1968
57/M 5 cases (37-61) 22/F
Abdominal NR Abdominal
pain
1973 1976
15 NR 10
Subtotal distal pancreatectomy Enuclearion NR u%ipple Whipple NR
pain
pain
10 7
20
Ishikawa et al.” Cubilla and Fitzgerald3 Allen et aI.l8
1981 1984
44/M 2 adult cases
Abdominal NR
pain
8 NR
1990
46/M
Abdominal
pain
18
Pereira-Limalg de LUava et al.“’
1991 1993
29/F 71/M
8.5 3.6
Ishii et aLzl
1994
66/M
Current
cases
1996 1996
47/F 40/M
Gastrointestinal bleed Abdominal pain, weight loss Incidental ultrasonographic finding Palpable mass Abdominal pain
HPF, High
power
field;
4.5 10 6
Subtotal distal pancreatectomy Whipple Subtotal distal pancreatectomy Chemotherapy only Whipple Whipple
NR, not reported
the common bile duct, and abutting the duodenal wall without invading it. The surgical margins were involved, with a 3 cm stump of normal pancreas distally. Nineteen resected peripancreatic lymph nodes were free of tumor. Microscopic examination revealed a solid but vascular spindle cell tumor with occasional entrapped pancreatic islets and a fibrous pseudocapsule. Areas with a storiform pattern alternated with patterns of intersecting fascicles (Fig. 2). Myxoid change was present focally. Necrosis was absent, but acute and chronic inflammatory cells were occasionally noted. Some enlarged, angulated vascular spaces were present focally. Most of the cells were uniform and fusiform with moderately eosinophilic, vaguely fibrillar cytoplasm. The nuclei were generally elongated, lacked distinct nucleoli, and had rounded ends and a stippled chromatin pattern. In a few areas the nuclei were somewhat larger and more pleomorphic, but no
epithelioid areas, giant cells, or bizarre nuclei were noted. The mitotic rate averaged two mitoses per high power field, with foci showing up to five mitoses per high power field. Immunohistochemical staining for markers of epithelial (cytokeratin), neural (S-100)) smooth muscle (actin, desmin), neuroendocrine (chromogranin), and endothelial (factor VIII, Ulex europaeus lectin, CD31, CD34) differentiation was negative. Stain for vimentin was strongly positive. Electron microscopy showed spindle-shaped tumor cells with complex interdigitating cell processes and well-formed, intermediatetype cell junctions. No desmosomes, microvilli, or cilia were seen. No external lamina was identified between cells. The cytoplasm was notable for numerous intermediate filaments. Rare subplasmalemmal dense bodies were identified, consistent with myoflbroblastic differentiation.
St1 rgq
Whme
Owen, 122,
Number
Madden,
Clmien
109
1
In2 m.u nosta,ining
,Vucleus grade
NR
NR
NR
0
Fibrosarcoma Spindle cell sarcoma
NR NR
NR NR
NR NR
NR Died/l
Reticulum
Frequent
NR
NR
Died/‘16
Leiomyosarcoma Leiomyosarcoma Sarcoma
Few Rare NR
NR NR NR
NR NR NR
0
Died/ 11 mo Died/l9 mo
Leiomyosarcoma Fibrosarcoma
NR NR
NR NR
NR NR
NR Alive, 8 yr
Fibrosarcoma
NR
NR
NR
L%lire, 11 yr
Fibrosarcoma Leiomyosarcoma (4 cases), NR (1) Myxofibrosarcoma vs fibrous histiocytoma Leiomyosarcoma Leiomyosarcoma, malignant hemangiopericytoma Malignant fibrous histiocytoma
Low NR NR
NR NR NR
NR NR LOI\,
Died, 1-14 mo Died, 17 mo
O-l/ 10 HPF NR
NR NR
NR NR
Died, 4 ?T NR
NR
NR
Died, 5 mo
Nerve sheath stromal cell tumor Leiomyosarcoma
NR lo-la/10
NR NR
Died, 1 yr NR
Leiomyosarcoma
>lO,/lO
High
Died, 21 mo
Spindle Spindle
O-5/10 HPF lO/‘lO HPF
Low Low
.Uive, 30 mo Alive, 10 JT
Disease
Spindle
cell carcinoma
cell sarcoma
cell stromal tumor cell stromal tumor
Mtotic I-ate
HPF HPF
The patient returned to full-time employment 1 month after operation. After 2 years of follow-up she remained symptom free and without evidence of local recurrence or metastatic disease by conventional radiograph and CT scan. Case 2. h 40-year-old white man with past history of moderate alcohol use and chronic recurrent pancreatitis presented with acute epigastric pain with nausea, vomiting, and hyperamylasemia (serum amylase, 306 units/dl). Abdominal CT scan demonstrated changes consistent with mild acute pancreatitis and a 6 x 7 cm mass in the head of the pancreas. Endoscopic retrograde cholangiopancreatography demonstrated extrinsic compression of the first and second portions of the duodenum and the main pancreatic duct. There was no compression of the distal common bile duct. Bile duct brushings yielded no cytologic evidence of malignancy. After 6
+
Survival/ follow-,llp
2 mo
mo
2 y-
weeks of bowel rest by means of total parenteral hyperalimentation, the patient underwent pancreatoduodenectomy without preservation of the pylorus (Whipple operation). At operation the head of the pancreas was distorted by a solid mass that was resected together with a 2 cm stump of normal pancreas. He received 3 units of packed red blood cells. The patient was discharged on postoperative day 13. Microscopic examination showed a tumor consisting of atypical spindle-cell smooth muscle cells arranged in sweeping fascicles and nests, with prominent vascular spaces (Fig.3). The tumor infiltrated among pancreatic acini in the resected pancreatic head and partially involved smooth muscle in the ampullary region. There was a maximum of 10 mitoses per high power field. Occasional giant nuceli were present. Immunohistochemical stains for S-100, keratin, factor VIII,
110
Ozuen, Madden,
Clmien
CD31, and CD34 were negative; stains for desmin, smooth muscle actin, and vimentin were positive.Two resected peripancreatic lymph nodes were free of tumor. The patient remained asymptomatic 10 years after operation. There has been no evidence of local recurrence or metastasis on yearly follow-up including a recent CT scan and chest x-ray film.
DISCUSSION While presenting with distinct symptoms and signs, the two patients discussedhere were treated by means of pancreatoduodenectomy for nonepithelial spindle-cell neoplasms in the head of the pancreas. Despite the substantial size of the tumors and the presence of moderate mitotic activity and cellular atypia, all features predictive of malignant behavior in soft tissue neoplasms elsewhere in the gastrointestinal tract and retroperitoneum,” both patients experienced a favorable outcome after curative resection. Trendelenburg probably performed the first surgical excision of a “spindle cell sarcoma” of the pancreas in 1882,5 and Segre gave the first pathologic description of two casesof primary sarcoma of the pancreas.6 The earlier literature consists of sporadic case reports, and it is difficult to discern the true pathologic diagnosis of many of these reports because of confusion among primary sarcomas of the pancreas, sarcomas of local or distant structures that involve the pancreas, and various forms of lymphoma. A literature review located 24 casesof pancreatic sarcoma consistent with a spindle cell structure reported since 1935l, 3, 5-22(Table II). These include tumors classifiedm in the original reports as leiomyosarcoma,3, g-11,l’* *O, 21 fibrous histiocyloma, l8 fibrosarcoma,*” 13-15hemangiopericytoma,” nerve sheath stromal tumor,lg spindle cell sarcoma,6,* reticulum cell tum0r,5 or simply asmesenchvmal tumor.16 The clinical presentation and outcome in these caseswere often not mentioned or highly variable ranging from slow growing and low-grade malignancies to more aggressive tumors that present with metastatic disease.Of note, prolonged survival wasreported in two casestreated by pancreatoduodenectomy.13, l5 The histologic and immunohistochemical findings in both casespresented here clearly indicate a nonepithelial origin, with features suggestive of smooth muscle or myofibroblastic differentiation, despite absent immunohistochemical reactivity for smooth muscle markers in one of the two cases.In both casesthe epicenter of the tumor was within the pancreatic head; the gross appearance and
Surgmy Ju$1997
presence of entrapped pancreatic elements support an anatomic origin in the head of the pancreas or proximal extrahepatic biliary duct system rather than in the bowel wall. In addition, in the second case pathologic examination showed ampullary involvement as well, leaving open the possibility that this tumor may have arisen in proximity to the duodenum and extended retrograde to involve the pancreatic head. For spindle cell neoplasms with morphologic affinity to smooth muscle arising in the alimentary tract, the term gastrointestinal stromal tumor (GIST) is currently preferred.” Some but not all GISTS exhibit immunochemical evidence of smooth muscle differentiation, and the clinical behavior of these neoplasms differs from that of smooth muscle tumors at other sites.The use of the analogously noncommital term pancreatic stromal tumor for the neoplasms reported here has the advantage of intimating their uncertain histogenesis, a conceivable clinical and pathologic parallel with GIST, and the likelihood that at least some of these tumors actually do arise initially in the intramural portion of the pancreatic duct system, as in the second case presented here. Pereira-Lima et al.lg first used the term pancreatic stromal tumor to refer to a spindle cell neoplasm of the head of the pancreas that showed variable reactivity for S100 protein and was therefore argued to be of nerve sheath origin. A substantial minority of GISTS also exhibit S-100 positivity, although it is debatable whether these should properly be considered schwannomas. If the criteria used for assessingmalignancy in GIST were applied to the lesions reported here, the mitotic rates would place them in the category of malignant tumors, whereas the large sizewould alsofavor a malignant diagn0sis.l As a result of the wide variations in tumor characteristics and methods of reporting, the isolated reports do not provide a sufficiently large experience to draw clear conclusions regarding the likely future behavior of similar tumors in other patients. Furthermore, no data exist that suggest that adjuvant radiation or chemotherapy might decrease the risk of local or distant recurrence of disease in patients with complete surgical resection. Like other soft tissue tumors of the gastrointestinal tract, surgical therapy remains the mainstay of therapy in patients with sarcomas arising from the pancreas. On the basisof our two casesand two other previous reports,13, l5 resection with wide tumor margin can be curative in some cases. In summary, two cases of large, pathologically malignant stromal tumors presenting in the head of the pancreas were successfully treated by means
Owen, Madden,
of pancreatoduodenectomy. Both patients remained alive 2 years and 10 years after operation, with no sign of either locally recurrent or distant metastatic disease. Similar cases have been reported with occasional prolonged survival after complete wrgical resection, which should remain the mainstay of therapy when feasible. These rare pancreatic tumors may thus represent a particular entiq amenable to curative therapy by surgery. REFERENCES 1. Baylor SAC,BergJu’. Croswdasdication and surviml characteristics of 5,000 cases of cancer of the pancreas. Surg Oncol1973;5:33558. 2. Elliott TE, Albertazzi 13, Lawence AD. Pancreatic liposarcoma Cancer 198O$1720-3. 3. Cubiia Lx Fiagemld PJ. Tumors of the exocrine pancreas. In: Hanman WH, Sobii LH, editors. Atlas of tumor pathology 2nd ed. Bethesda (MD):;\rmedForceslnstinlteofPathol~!; 1984. p 22@48. 4. Franquemont DW Differentiation and risk assessment of gastrointestional stromal tumors. Am J Clin Path01 1995;103:41-7. 5. Feather HE, Kuhn CL. Total pancreatectomy for sarcoma of the pancreas. Ann Surg 1951;134:904-12. 6. Oesterlin EJ, Blumenthal RW. Spindle cell sarcoma of the pancreas. Am J Med Sci 1935;289:i84-9. Are1 F. Rare tumors: etiology and localization. J Int Co11 Surg 1949;12:G73-4. Brunschwig .I. Radical pancreatectomy and splenectomy ivith left pneumectomy at one sitting for sarcoma of the pancreas and pulmonary metastases. Cancer 1949;2:576-80. Ross CF. Leiomyosarcoma of the pancreas. Br J Surg 1951;39:53-6.
Chien
111
10. Judd CS, Hill RL. Pancreaticoduodenectomy for leiomyosarcoma of the duodenum. Ann Surg 1954;139:103-20. 11. Becker MT, Welsh RA, Pratt HS. Cystadenoma and cystadenocarcinoma of the pancreas. .Snn Surg 1965;161:845-63. 12. Berman JK, Levene N. Sarcoma of the pancreas. Arch Surg 1965;73:894-6. 13. Brooke WS, Max-well JG. Primary sarcoma of the pancreas: eight years survival after pancreaticoduodenectomy ;\m J Surg 1966;112:657-61. 14. Chevrel B. Sarcome de pan&as. Ann Chir 1968;22:199203. 15. Neibling HA. Primary sarcoma of the pancreas. Am Surg 1968;34:690-3. 16. hfargules RhI, .Wen R, Dunphy JE. Pancreatic tumor of mesenchynal origin presenting as obstructive jaundice. Am J Surg 1976;131:357-9. 17. Ishikawa 0, Iwanaga T, Matisui U, Terasawa T, M’ada A. Leiomyosarcoma of the pancreas. Am J Path01 1951;5:597-602. IS. Allen I(, Skandalakis L, Brown B, Gray S, Skandalakis J. Malignant fibrous histiocytoma of the pancreas. Am Surg 1990;56:36&8. 19. Per&a-Lima L, Kalil A, Furian MB. Pancreatic stoma1 tumor of nerve sheath origin treated by pancreatoduodenectomy. HPB Surg 1991;4:165-9. 20. de ;Uava E, Tarramade J, Vazquez JJ. Leiomyosarcoma of the pancreas. Virchows Arch Path01 Anat Histopathol 1993;422:419-22. N, Nose H, Yoshimori M, Aoki K, 21. Ishii H, Okada S. Okazaki et al. Leiom>osarcoma of the pancreas: report of a case diagnosed by fine needle aspiration biopsy. Jpn J Clin Oncol 1994;24:42-5. 22. Enzinger FM, ‘i\‘eiss SW. Soft tissue tumors. 3rd ed. St Louis: Mosb!; 1995.
reports
Spindle cell stromal tumor pancreas: Treatment by pancreatoduodenectomy Clarence
From Duke
H. Owen,
MD,
John
the Division of Hepatobiliary Universit~l AIedical Center;
F. Madden,
Swgery Durham,
MD,
PhD,
and Liver N C.
OF THE p.wcmks is rare, and criteria for classification and prognosis are less firmly established than for similar tumors at other sites in the gastrointestinal tract. Sarcomas comprise less than 0.1% of pancreatic malignancies overall, and in a large review of 5075 histologically confirmed primary pancreatic malignancies collected between 1955 and 1969, only five sarcomas were f0und.l A few case reports concern distinctive sarcoma subtypes such as liposarcoma,’ rhabdomyosarcoma, or osteogenic sarcoma,3 but the largest group of cases in both the older and recent literature appear to be sarcomas with a spindle cell structure. These are most often classified as leiomyosarcoma, although definitive evidence of smooth muscle differentiation has not always been provided in these reports. We recently encountered an unusual case of a primary spindle cell neoplasm that appeared to arise primarily in the head of the pancreas. Despite the large size of the tumor at presentation and histologic features compatible with malignancy, the history suggested an indolent rate of growth. The tumor was completely resected by means of pancreatoduodenectomy and the patient remained free of disease 2 years after operation. A review of our surgical records located a second case in which a spindle cell stromal tumor presenting clinically as a pancreatic head mass and pathologically S.MCOM.A
;2ccepted
for publication
1997;122:10511. Q 1997 by Mosby-l’ear
0039-6060,/97,:$5.00+0
Trans$a~~tati.o~~,
Clavien,
Departments
MD,
of Sulgry
PhD,
Dzu%zm,
AT C.
and PathoLog?,
involving the pancreatic head was similarly resected with apparent cure. Here we report both cases and review the literature regarding presentation, classification, therapy, and prognosis of primary spindle cell neoplasms of the pancreas. METHODS Surgical pathology reports of 337 surgical resections and open and percutaneous needle biopsies of pancreatic masses, representing all such material examined pathologically at Duke University Medical Center from 1979 until 1995, were reviewed (Table I). In seven cases (2.1%) the pathologic diagnosis was sarcoma involving the pancreas. Histologic material and patient records were reviewed. Two patients (0.6% of all pancreas specimens) had a spindle cell neoplasm that presented clini-
Sept. 9, 1996.
Reprint requests: Pierre A. Clavien, MD, PbD, Associate Chief, Hepato-Bilk-y Surgery & Liver Transplantation, Duke University Medical Center. Durham, NC 27710. Surgery Copyighr
and Pierre-Alain
of the
Book,
11/'57/79769
Inc.
Professor, Box 3247, Fig. 1. Axial CT images mass arising from head periaortic Iymphadenopathy mesenteric artery.
demonstrate large, hypervascular of pancreas with no suggestion of or encasement of superior
SURGERY
105
106
SUTgXT~ July 1997
Owen, Madden, Clavien
Fig. 2. Tumor histology is characterized by interlacing fascicles of spindle cells with scattered, dilated vascular spaces (case 1) (A, hematoxylin-eosin stain; original magni!Zcation x100). High power view shows fairly uniform nuclear structure with occasional mitoses (B, hematoxylineosin stain; original magnilication x400).
Table I. Pancreas neoplasms at Duke University Medical Center between 1979 and 1995”
Carcinoma Neuroendocrine neoplasm Ampullary carcinoma Cystic neoplasm Lymphoma Sarcoma Total “Derived from and incidental
No. of cases
Percent of total
229 32 28 25 15 2 331
69.2 9.7 8.5 7.6 4.5 0.6
total of 67‘2 specimens excluding pancreatitis benign pancrks biopsies (n = 62).
(n = 274)
tally as a pancreatic head massand are presented in detail below. In the remaining casesthe tumor arose clinically from nearby structures (malignant stromal tumor of the stomach, one case, and of the duodenum, three cases)and involved the pancreas secondarily or represented a metastasis from a remote site (malignant fibrous histiocytoma of the scapula, one case). In one additional case a highgrade sarcomatoid
malignancy
of the pancreatic
head
resembling malignant fibrous histiocytoma showed immunohistochemical reactivity for cytokeratin and wastherefore classifiedasprobable sarcomatoid carci-
surgery Volume
Owen, Madden, 122, Number
Clauien
107
1
Fig. 3. Tumor infiltrates between pancreatic acini (case 2) (A, hematoxylin-eosin stain; original magnification x170). High power shows pleomorphic spindle cells with fibrillar cytoplasm and blunt-ended nuclei, fairly uniform nuclear structure with occasional mitoses (B, hematoxylin-eosin stain; original magnification x520).
noma, even though
electron
microscopic
examination
failed to discloseevidence of epithelial derivation. CASE REPORTS Case 1. A 47-year-old white woman presented to her local physician with a palpable mass in the right upper quadrant. The patient reported a sense of fullness in the area for several years, but there were no other symptoms. Laboratory examination disclosed mild anemia (hemoglobin, 8.4 gm/dl) and liver dysfunction (aspartate aminotransferase, 115 units/l; alanine aminotransferase, 102 units/l; alkaline phosphatase, 140 units/L) without jaundice (total bilirubin, 0.3 mg/dl). An abdominal computed tomography (CT) scan
revealed a large, hypervascular mass in the right upper quadrant associated with the head of the pancreas and the right lobe of the liver and extending across the midline (Fig. I). An arteriogram showed the vascular supply horn the gastroduo denal and superior mesenteric arteries. At laparotomy an 11 x 10 x 9 cm, solid mass was found in the head of the pancreas displacing the surrounding duodenum, liver, stomach, and colon. Pancreatoduodenectomy was performed without preservation of the pylorus (Whipple operation). Blood transfusion was not required. The patient had an uneventful recovery and was discharged home on postoperative day 11. Gross examination of the resected specimen showed the mass distorting the head of the pancreas, encasing
108
Grgery July 1997
Owen, Madden, Clavien
Table II. Summary of 26 casesconsistent with diagnosis of primary spindle cell stromal tumor of the pancreas Clinical presenta.tion
Authm
Yea.r
Oesterlin and Blumenthal’
1935
57/F
Arel’ Brunschwigs
1949
1949
Feather and Kuhn5 Ross9 Judd and Hill” Berman and Levene’? Becker et al.” Brooke and Maxwell1s Neibling’” Chevrel’” Baylor and Berg’ Margules et a1.16
Operation
7
Laparotomy
48/M 37/M
Weight loss, painless jaundice Abdominal pain Abdominal pain
5 8
1951
29/M
Abdominal
6
1951 1954 1956
80/M 31/M 47/M
Palpable mass Gastrointestinal bleed Painless jaundice
5.5
Enucleation Subtotal distal pancreatopneumectomy Total pancreatectomy None Whipple Whipple
1965 1966
NR 44/M
NR 6
NR Whipple
1968
29iF
NR Abdominal pain, jaundice Palpable mass
1968
57/M 5 cases (37-61) 22/F
Abdominal NR Abdominal
pain
1973 1976
15 NR 10
Subtotal distal pancreatectomy Enuclearion NR u%ipple Whipple NR
pain
pain
10 7
20
Ishikawa et al.” Cubilla and Fitzgerald3 Allen et aI.l8
1981 1984
44/M 2 adult cases
Abdominal NR
pain
8 NR
1990
46/M
Abdominal
pain
18
Pereira-Limalg de LUava et al.“’
1991 1993
29/F 71/M
8.5 3.6
Ishii et aLzl
1994
66/M
Current
cases
1996 1996
47/F 40/M
Gastrointestinal bleed Abdominal pain, weight loss Incidental ultrasonographic finding Palpable mass Abdominal pain
HPF, High
power
field;
4.5 10 6
Subtotal distal pancreatectomy Whipple Subtotal distal pancreatectomy Chemotherapy only Whipple Whipple
NR, not reported
the common bile duct, and abutting the duodenal wall without invading it. The surgical margins were involved, with a 3 cm stump of normal pancreas distally. Nineteen resected peripancreatic lymph nodes were free of tumor. Microscopic examination revealed a solid but vascular spindle cell tumor with occasional entrapped pancreatic islets and a fibrous pseudocapsule. Areas with a storiform pattern alternated with patterns of intersecting fascicles (Fig. 2). Myxoid change was present focally. Necrosis was absent, but acute and chronic inflammatory cells were occasionally noted. Some enlarged, angulated vascular spaces were present focally. Most of the cells were uniform and fusiform with moderately eosinophilic, vaguely fibrillar cytoplasm. The nuclei were generally elongated, lacked distinct nucleoli, and had rounded ends and a stippled chromatin pattern. In a few areas the nuclei were somewhat larger and more pleomorphic, but no
epithelioid areas, giant cells, or bizarre nuclei were noted. The mitotic rate averaged two mitoses per high power field, with foci showing up to five mitoses per high power field. Immunohistochemical staining for markers of epithelial (cytokeratin), neural (S-100)) smooth muscle (actin, desmin), neuroendocrine (chromogranin), and endothelial (factor VIII, Ulex europaeus lectin, CD31, CD34) differentiation was negative. Stain for vimentin was strongly positive. Electron microscopy showed spindle-shaped tumor cells with complex interdigitating cell processes and well-formed, intermediatetype cell junctions. No desmosomes, microvilli, or cilia were seen. No external lamina was identified between cells. The cytoplasm was notable for numerous intermediate filaments. Rare subplasmalemmal dense bodies were identified, consistent with myoflbroblastic differentiation.
St1 rgq
Whme
Owen, 122,
Number
Madden,
Clmien
109
1
In2 m.u nosta,ining
,Vucleus grade
NR
NR
NR
0
Fibrosarcoma Spindle cell sarcoma
NR NR
NR NR
NR NR
NR Died/l
Reticulum
Frequent
NR
NR
Died/‘16
Leiomyosarcoma Leiomyosarcoma Sarcoma
Few Rare NR
NR NR NR
NR NR NR
0
Died/ 11 mo Died/l9 mo
Leiomyosarcoma Fibrosarcoma
NR NR
NR NR
NR NR
NR Alive, 8 yr
Fibrosarcoma
NR
NR
NR
L%lire, 11 yr
Fibrosarcoma Leiomyosarcoma (4 cases), NR (1) Myxofibrosarcoma vs fibrous histiocytoma Leiomyosarcoma Leiomyosarcoma, malignant hemangiopericytoma Malignant fibrous histiocytoma
Low NR NR
NR NR NR
NR NR LOI\,
Died, 1-14 mo Died, 17 mo
O-l/ 10 HPF NR
NR NR
NR NR
Died, 4 ?T NR
NR
NR
Died, 5 mo
Nerve sheath stromal cell tumor Leiomyosarcoma
NR lo-la/10
NR NR
Died, 1 yr NR
Leiomyosarcoma
>lO,/lO
High
Died, 21 mo
Spindle Spindle
O-5/10 HPF lO/‘lO HPF
Low Low
.Uive, 30 mo Alive, 10 JT
Disease
Spindle
cell carcinoma
cell sarcoma
cell stromal tumor cell stromal tumor
Mtotic I-ate
HPF HPF
The patient returned to full-time employment 1 month after operation. After 2 years of follow-up she remained symptom free and without evidence of local recurrence or metastatic disease by conventional radiograph and CT scan. Case 2. h 40-year-old white man with past history of moderate alcohol use and chronic recurrent pancreatitis presented with acute epigastric pain with nausea, vomiting, and hyperamylasemia (serum amylase, 306 units/dl). Abdominal CT scan demonstrated changes consistent with mild acute pancreatitis and a 6 x 7 cm mass in the head of the pancreas. Endoscopic retrograde cholangiopancreatography demonstrated extrinsic compression of the first and second portions of the duodenum and the main pancreatic duct. There was no compression of the distal common bile duct. Bile duct brushings yielded no cytologic evidence of malignancy. After 6
+
Survival/ follow-,llp
2 mo
mo
2 y-
weeks of bowel rest by means of total parenteral hyperalimentation, the patient underwent pancreatoduodenectomy without preservation of the pylorus (Whipple operation). At operation the head of the pancreas was distorted by a solid mass that was resected together with a 2 cm stump of normal pancreas. He received 3 units of packed red blood cells. The patient was discharged on postoperative day 13. Microscopic examination showed a tumor consisting of atypical spindle-cell smooth muscle cells arranged in sweeping fascicles and nests, with prominent vascular spaces (Fig.3). The tumor infiltrated among pancreatic acini in the resected pancreatic head and partially involved smooth muscle in the ampullary region. There was a maximum of 10 mitoses per high power field. Occasional giant nuceli were present. Immunohistochemical stains for S-100, keratin, factor VIII,
110
Ozuen, Madden,
Clmien
CD31, and CD34 were negative; stains for desmin, smooth muscle actin, and vimentin were positive.Two resected peripancreatic lymph nodes were free of tumor. The patient remained asymptomatic 10 years after operation. There has been no evidence of local recurrence or metastasis on yearly follow-up including a recent CT scan and chest x-ray film.
DISCUSSION While presenting with distinct symptoms and signs, the two patients discussedhere were treated by means of pancreatoduodenectomy for nonepithelial spindle-cell neoplasms in the head of the pancreas. Despite the substantial size of the tumors and the presence of moderate mitotic activity and cellular atypia, all features predictive of malignant behavior in soft tissue neoplasms elsewhere in the gastrointestinal tract and retroperitoneum,” both patients experienced a favorable outcome after curative resection. Trendelenburg probably performed the first surgical excision of a “spindle cell sarcoma” of the pancreas in 1882,5 and Segre gave the first pathologic description of two casesof primary sarcoma of the pancreas.6 The earlier literature consists of sporadic case reports, and it is difficult to discern the true pathologic diagnosis of many of these reports because of confusion among primary sarcomas of the pancreas, sarcomas of local or distant structures that involve the pancreas, and various forms of lymphoma. A literature review located 24 casesof pancreatic sarcoma consistent with a spindle cell structure reported since 1935l, 3, 5-22(Table II). These include tumors classifiedm in the original reports as leiomyosarcoma,3, g-11,l’* *O, 21 fibrous histiocyloma, l8 fibrosarcoma,*” 13-15hemangiopericytoma,” nerve sheath stromal tumor,lg spindle cell sarcoma,6,* reticulum cell tum0r,5 or simply asmesenchvmal tumor.16 The clinical presentation and outcome in these caseswere often not mentioned or highly variable ranging from slow growing and low-grade malignancies to more aggressive tumors that present with metastatic disease.Of note, prolonged survival wasreported in two casestreated by pancreatoduodenectomy.13, l5 The histologic and immunohistochemical findings in both casespresented here clearly indicate a nonepithelial origin, with features suggestive of smooth muscle or myofibroblastic differentiation, despite absent immunohistochemical reactivity for smooth muscle markers in one of the two cases.In both casesthe epicenter of the tumor was within the pancreatic head; the gross appearance and
Surgmy Ju$1997
presence of entrapped pancreatic elements support an anatomic origin in the head of the pancreas or proximal extrahepatic biliary duct system rather than in the bowel wall. In addition, in the second case pathologic examination showed ampullary involvement as well, leaving open the possibility that this tumor may have arisen in proximity to the duodenum and extended retrograde to involve the pancreatic head. For spindle cell neoplasms with morphologic affinity to smooth muscle arising in the alimentary tract, the term gastrointestinal stromal tumor (GIST) is currently preferred.” Some but not all GISTS exhibit immunochemical evidence of smooth muscle differentiation, and the clinical behavior of these neoplasms differs from that of smooth muscle tumors at other sites.The use of the analogously noncommital term pancreatic stromal tumor for the neoplasms reported here has the advantage of intimating their uncertain histogenesis, a conceivable clinical and pathologic parallel with GIST, and the likelihood that at least some of these tumors actually do arise initially in the intramural portion of the pancreatic duct system, as in the second case presented here. Pereira-Lima et al.lg first used the term pancreatic stromal tumor to refer to a spindle cell neoplasm of the head of the pancreas that showed variable reactivity for S100 protein and was therefore argued to be of nerve sheath origin. A substantial minority of GISTS also exhibit S-100 positivity, although it is debatable whether these should properly be considered schwannomas. If the criteria used for assessingmalignancy in GIST were applied to the lesions reported here, the mitotic rates would place them in the category of malignant tumors, whereas the large sizewould alsofavor a malignant diagn0sis.l As a result of the wide variations in tumor characteristics and methods of reporting, the isolated reports do not provide a sufficiently large experience to draw clear conclusions regarding the likely future behavior of similar tumors in other patients. Furthermore, no data exist that suggest that adjuvant radiation or chemotherapy might decrease the risk of local or distant recurrence of disease in patients with complete surgical resection. Like other soft tissue tumors of the gastrointestinal tract, surgical therapy remains the mainstay of therapy in patients with sarcomas arising from the pancreas. On the basisof our two casesand two other previous reports,13, l5 resection with wide tumor margin can be curative in some cases. In summary, two cases of large, pathologically malignant stromal tumors presenting in the head of the pancreas were successfully treated by means
Owen, Madden,
of pancreatoduodenectomy. Both patients remained alive 2 years and 10 years after operation, with no sign of either locally recurrent or distant metastatic disease. Similar cases have been reported with occasional prolonged survival after complete wrgical resection, which should remain the mainstay of therapy when feasible. These rare pancreatic tumors may thus represent a particular entiq amenable to curative therapy by surgery. REFERENCES 1. Baylor SAC,BergJu’. Croswdasdication and surviml characteristics of 5,000 cases of cancer of the pancreas. Surg Oncol1973;5:33558. 2. Elliott TE, Albertazzi 13, Lawence AD. Pancreatic liposarcoma Cancer 198O$1720-3. 3. Cubiia Lx Fiagemld PJ. Tumors of the exocrine pancreas. In: Hanman WH, Sobii LH, editors. Atlas of tumor pathology 2nd ed. Bethesda (MD):;\rmedForceslnstinlteofPathol~!; 1984. p 22@48. 4. Franquemont DW Differentiation and risk assessment of gastrointestional stromal tumors. Am J Clin Path01 1995;103:41-7. 5. Feather HE, Kuhn CL. Total pancreatectomy for sarcoma of the pancreas. Ann Surg 1951;134:904-12. 6. Oesterlin EJ, Blumenthal RW. Spindle cell sarcoma of the pancreas. Am J Med Sci 1935;289:i84-9. Are1 F. Rare tumors: etiology and localization. J Int Co11 Surg 1949;12:G73-4. Brunschwig .I. Radical pancreatectomy and splenectomy ivith left pneumectomy at one sitting for sarcoma of the pancreas and pulmonary metastases. Cancer 1949;2:576-80. Ross CF. Leiomyosarcoma of the pancreas. Br J Surg 1951;39:53-6.
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10. Judd CS, Hill RL. Pancreaticoduodenectomy for leiomyosarcoma of the duodenum. Ann Surg 1954;139:103-20. 11. Becker MT, Welsh RA, Pratt HS. Cystadenoma and cystadenocarcinoma of the pancreas. .Snn Surg 1965;161:845-63. 12. Berman JK, Levene N. Sarcoma of the pancreas. Arch Surg 1965;73:894-6. 13. Brooke WS, Max-well JG. Primary sarcoma of the pancreas: eight years survival after pancreaticoduodenectomy ;\m J Surg 1966;112:657-61. 14. Chevrel B. Sarcome de pan&as. Ann Chir 1968;22:199203. 15. Neibling HA. Primary sarcoma of the pancreas. Am Surg 1968;34:690-3. 16. hfargules RhI, .Wen R, Dunphy JE. Pancreatic tumor of mesenchynal origin presenting as obstructive jaundice. Am J Surg 1976;131:357-9. 17. Ishikawa 0, Iwanaga T, Matisui U, Terasawa T, M’ada A. Leiomyosarcoma of the pancreas. Am J Path01 1951;5:597-602. IS. Allen I(, Skandalakis L, Brown B, Gray S, Skandalakis J. Malignant fibrous histiocytoma of the pancreas. Am Surg 1990;56:36&8. 19. Per&a-Lima L, Kalil A, Furian MB. Pancreatic stoma1 tumor of nerve sheath origin treated by pancreatoduodenectomy. HPB Surg 1991;4:165-9. 20. de ;Uava E, Tarramade J, Vazquez JJ. Leiomyosarcoma of the pancreas. Virchows Arch Path01 Anat Histopathol 1993;422:419-22. N, Nose H, Yoshimori M, Aoki K, 21. Ishii H, Okada S. Okazaki et al. Leiom>osarcoma of the pancreas: report of a case diagnosed by fine needle aspiration biopsy. Jpn J Clin Oncol 1994;24:42-5. 22. Enzinger FM, ‘i\‘eiss SW. Soft tissue tumors. 3rd ed. St Louis: Mosb!; 1995.