Annals of Diagnostic Pathology 17 (2013) 372–376

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Annals of Diagnostic Pathology

Gastrointestinal stromal tumor of the ampulla of Vater with osteoclastic giant cells,osteoid-like matrix deposition, and aneurysmal bone cyst-like features☆

Fernando Candanedo-Gonzalez MD, MsC a,⁎, Leslie Camacho-Rebollar MD a,Candelaria Cordova Uscanga MD a, Alejandra Romero Utrilla MD a, Maria Eugenia Palmerin Bucio MD a,Sandra Sanchez Rodriguez MD a, Luis Mora Hernandez MD b

a Department of Pathology, Oncology Hospital, National Medical Center Century XXI. I.M.S.S., Mexico City, Mexicob Department of Radiology, Oncology Hospital, National Medical Center Century XXI. I.M.S.S., Mexico City, Mexico

☆ Conflict of interest: The authors declare that theyinterest which would warrant disclosure.⁎ Corresponding author. Tel.: +52 5627 6900x22733

E-mail address: fcandanedo@hotmail.com (F. Canda

1092-9134/$ – see front matter © 2013 Elsevier Inc. Alhttp://dx.doi.org/10.1016/j.anndiagpath.2012.08.003

a b s t r a c t

a r t i c l e i n f o

Keywords:

Gastrointestinal stromal tumorOsteoclast-like giant cellOsteoid-like materialAneurismal bone cyst-likeAmpulla of Vater

Gastrointestinal stromal tumors are a heterogeneous group with a wide spectrum of histologic features. Wedescribe the first case of 61-year-old womanwho presented gastrointestinal stromal tumors of the ampulla ofVater with osteoclast-like giant cells surrounding osteoid-like material and aneurismal bone cyst-like areas.The phenotype was supported by light microscopy and corroborated by immunohistochemistry analysis.Because of the presence of osteoid-like and aneurismal bone cyst-like components, it is first necessary tomake differential diagnosis with other entities such as metastatic osteosarcoma. Our case shows another formof differentiation that has not previously been reported.

have no potential conflicts of

.nedo-Gonzalez).

l rights reserved.

© 2013 Elsevier Inc. All rights reserved.

1. Introduction

Gastrointestinal stromal tumors (GISTs) are rare neoplasms thataccount for 1% of all gastrointestinal malignancies. Gastrointestinalstromal tumors are mainly located in the stomach, small bowel, andcolon [1]. Duodenal localization is rare, accounting for approximately4% of all cases [2]. However, primary GIST of the periampullaryregion is exceedingly rare [3]. Gastrointestinal stromal tumors arecommonly composed of spindle and sometimes epithelioid cells.However, GIST showed a remarkable variability in their differenti-ation pathways. Therefore, immunohistochemistry is necessarybecause most GISTs are positive for c-kit protein (CD117) andCD34 [4].

On the other hand, the occurrence of osteoclast-like giant cells(OGCs) in extraskeletal tumors, although uncommon, is wellknown, particularly in malignant epithelial tumors such as OGCscarcinomas of the breast [5], pancreas [6], and other organs [7].Moreover, their presence, albeit rare, is well documented inleiomyosarcomas of the gastrointestinal tract and GIST [8,9]. Toour knowledge, in the English literature, only 4 cases of GIST withOGCs have been reported [8-11]. However, osteoid-like material inthese tumors has not previously been informed. Moreover, the

characteristics and biologic behavior of GIST with OGCs of theperiampullary region are not yet well understood. We report theclinicomorphological features of a GIST of the ampulla of Vater withOGCs, osteoid-like material, and aneurismal bone cyst-like areas in aMexican woman.

2. Case report

A 61-year-old Mexican woman presented with microcytichypochromic anemia for 15 years and wasting syndrome. Shewas treated with iron-rich diet and iron supplement as ferroussulfate. In April 2011, there was added abdominal pain in theepigastrium and hypogastrium, accompanied by weight loss of 5 kg,bloating, and dyspepsia. On physical examination, we found noevidence of jaundice, with normal peristalsis, without evidence ofperitoneal irritation. Abdominal computed tomographic scanshowed a mass between the second and third portion of duodenum(Fig. 1A); the mass infiltrated the wall of the duodenum withoutobstruction of the lumen. By endoscopy confirmed the presence oftumor in the ampulla of Vater; biopsies were taken, which wereinitially diagnosed as poorly differentiated adenocarcinoma. Serumcarcinoembryonic antigen level, chest x-ray examination findings,and colonoscopy were all unremarkable. An elective laparotomyand pancreaticoduodenectomy with lymph node dissection wereperformed. The tumor was removed completely with negativemargins. Because the patient had an uncomplicated postoperativeperiod, she was discharged. Six months later, the patient is alivefree of disease.

A

B

C

Fig. 1. Gastrointestinal stromal tumor. (A) Abdominal computed tomographic scanshows a mass between the second and third portion of duodenum. Gross appearanceshowed a ulcerated polypoid tumor in ampulla of Vater (B) and solid tumor invadingthe duodenal wall and respected the pancreas and pancreatic duct (arrow) (C).

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3. Pathologic findings

3.1. Gross findings

Macroscopically, the surgical specimens showed a polypoid tumorof the ampulla of Vater that measured 3 × 2.8 cm, invading theduodenal wall without invasion to the pancreas (Fig. 1B and C).

3.2. Microscopic findings

Microscopically, the tumor was ulcerated (Fig. 2A), composedmainly of spindle cells growing in fascicular pattern (Fig. 2B),storiform arrangements (Fig. 2C), and focal collections of skenoidfibers (Fig. 2D), which were intimately admixed with OGCs withosteoid-like material (Fig. 3A-E) and focal aneurismal bone cyst-likeareas with spaces separated by septa that contain blood (Fig. 3F). The

septa lack and endothelial lining and consist of spindle cells, giantcells, capillaries, and varying amounts of matrix. Mitotic figures werenot readily seen, and necrosis was not present.

3.3. Immunohistochemical findings

The specimen was fixed in 10% buffered formalin and paraffinembedded. Hematoxylin and eosin–stained sections were used fordiagnosis. Immunohistochemistry was performed on 5-μm sectionsfrom a representative block using the avidin-biotin-peroxidasecomplex method. Appropriate negative and positive controls werealso examined. The following antibodies were used: CD34, c-Kit(CD117), desmin, α-smoothmuscle actin, S-100 protein, CAM 5.2, andAE1/AE3, epithelial membrane antigen, p53, Ki-67, and histiocyte/macrophage marker CD68 (KP1).

Neoplastic cells were diffusely positive for CD117 (Fig. 4A-B) andCD34 (Fig. 4C). There was also a focal staining for α-smooth muscleactin (Fig. 4D) and S-100 protein (Fig. 4E). They were negative forcytokeratin, membrane epithelial antigen, and desmin. The OGCswere negative for all markers. Neoplastic cells showed a cellularproliferation index of 15% (Fig. 4F) and showed overexpression ofp53 (Fig. 4G).

4. Discussion

Gastrointestinal stromal tumor is an infrequent neoplasm with anannual incidence of 12.7 per million in the Netherlands and 6.8 permillion in the United States [12,13]. Gastrointestinal stromal tumorsare most commonly seen in the stomach (50%), followed by the smallintestine (25%), colon (10%), omentum/mesentery (7%), and theesophagus (5%) [1,14,15], although GIST located in the periampullaryregion is rare [2,3]. We report the second case of GIST with OGCs inperiampullary region. Kocer et al [10] were the first to report a case ofGIST with OGCs but with a synchronous well-differentiated neuroen-docrine tumor in the ampulla of Vater. On the other side, Do et al [11]report a GIST with OGCs and aneurismal bone cyst-like features.However, our case is the first described the osteoid-like materialalternating with aneurismal bone cyst-like areas. Table summarizesthe characteristics of all reported cases along with ours.

Gastrointestinal stromal tumors are a heterogeneous group with abroad spectrum of histologic features, typically including spindle orepithelioid cells growing in fascicular, storiform, palisading, syncytial,myxoid pattern and focal to extensive hyalinization [1]. Alvarado-Cabrero et al [16] studied a series of 275 patients with GIST from 3institutions in Mexico, including our own. They analyzed thehistologic features of each tumor and found that the cell type includedpure spindle (68%), pure epithelioid (16%), and mixed epithelioid/spindle cells (14%). They also analyzed the histologic grade andfinding that only 43% showed high-grade morphological characteris-tics. However, marked nuclear pleomorphism was uncommon, andnone of the cases presented OGCs. Miettinen et al [17] describedmarked focal pleomorphism in 4 of 37 colonic GISTs, and the originalillustration contained floret-type tumor giant cells with pleomorphicnuclei. Pasquinelli et al [18] described scattered multinucleated giantcells of unspecified type in 1 of 6 GISTs of the stomach. Unlike otherpreviously reported cases, our case shows a mixture of spindle cellsand numerous osteoclast-like multinucleated giant cells.

Moreover, the occurrence of OGCs, although uncommon, is welldocumented in GIST [8-10]. The unusual morphology of these tumorscaused significant diagnostic difficulties. In our case, the OGCs werefound immersed in and around varying amount of osteoid-likematerial and around areas resembling aneurysmal bone cyst.Therefore, we consider that the main differential diagnosis is withmetastatic osteosarcoma [19]. In this sense, Panizo-Santos et al [19]reported a case of metastatic osteosarcoma presenting as a polyptumor in jejunum. However, unlike our case, the tumor shows

A B

C D

Fig. 2. Gastrointestinal stromal tumor with OGCs. (A) Low-power view showed a tumor compressing the mucosa and ulcer. (B) High-power view showed typical GIST composed offascicles of spindle cells. (C) Some areas showed spindle cells arranged in a storiform pattern. (D) In other areas, there are deposition of amorphous eosinophilic extracellularcollections of skeinoid fibers (arrows) with low cellularity.

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osteoid with OGCs with pleomorphic nuclei, bizarre, and atypicalmitosis. Making differential diagnosis with these entities is importantbecause the prognosis and therapy are different. Then, clinicalcorrelation, sampling of the tumor and immunohistochemistry areuseful to rule out this possibility. By immunohistochemical stains,our case showed diffusely positivity for CD117 and CD34, and allepithelial markers and desmin were negative, which confirmedbeyond doubt that it is a GIST.

Although their cell of origin of GIST is not fully understood,resemblance to the interstitial cells of Cajal and expression of somesmooth muscle markers suggest origin from multipotential cells thatcan differentiate into Cajal and smooth muscle cells [20]. Our casesupports this idea, as showed dual differentiation that was evidentwith focal expression of smooth muscle actin and S-100 protein. Inaddition, there is evidence that GISTs can develop heterologouscomponents mainly rhabdomyoblasts differentiation. Specifically,after which patients received imatinib therapy [21]. However, ourcase showed osteoid-like differentiation, but the patient did notreceive imatinib before resection of the tumor.

In conclusion, GISTs of the ampulla of Vater may be a rare cause ofupper gastrointestinal bleeding. We show a variant not yet wellrecognized of GIST with OGCs, osteoid-like material, and aneurismalbone cyst-like features located in the ampulla of Vater that lends itselfto confusion in diagnosis. The presence of OGCs in GIST further widensits histologic spectrum. The tumor resembles giant cell tumor of bonebut by immunohistochemistry is positive for CD117 and CD34. Theirpresence should alert us to the possibility of GIST among otherdifferential diagnoses in the appropriate setting. We do not know anddo not have enough data to speculate whether the presence of OGCs isassociated with a different biological behavior. It was successfullytreated by a pancreaticoduodenectomy. Surgical resection remainsthe cornerstone of treatment for patients with localized disease.

Acknowledgments

The authors thank Oscar Martínez Quirarte and Juan Diaz Moralesfor their assistance in immunohistochemistry analysis.

References

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A B

D C

E F

Fig. 3. Gastrointestinal stromal tumor containing numerous multinucleated giant cells. (A to D) Sections of the GIST showed geographic areas of osteoid-like material and OGCs. (E)Osteoclast-like giant cells form sheets having many nuclei without pleomorphism. (F) High-power view spaces separated by septa that contain blood. Septa lacking endotheliallining and are surrounded by spindle cells, OGCs (arrow) and varying amounts of matrix.

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A B

F G

*

C D E

Fig. 4. Sections of the GIST with immunostaining. (A to B) Neoplastic cells are strongly positive for CD117, but osteoid-like material (asterisk) and OGCs (arrow) are negative. (C)Neoplastic cells are strongly positive for CD34, but osteoid (asterisk) are negative. Focal staining for α-smoothmuscle actin (D) and S-100 protein (E); neoplastic cells are positive forKi-67 (F); neoplastic cells are positive for p53 (G).

TableReported cases of GIST with OGCs

Ref Age (y) Sex Localization and some features Size (cm) Histology features Status

[8] 85 F Small intestine firm mural nodule withintact mucosa but showed infiltrativegrowth into the mesenteric fat

1.7 Acellular hyalinized areas AWD

[9] 68 F Descending colon 11.0 Epithelioid cells, small foci of necrosis,15 mitosis/50 HPF

Died of disease due to lung and abdominalmetastases, 6 mo after surgery

[10] 44 M Ampulla of Vater 6.5 Also found a WDNT near the GIST AWD[11] 67 M Proximal jejunum 2.5 Aneurysmal bone cyst-like AWDPresent case 61 F Ampulla of Vater 3.0 OGCs

Osteoid-likeAneurysmal bone cyst-like

AWD

Abbreviations: F, female; M, male; AWD, alive without disease; HPF, high-power fields; WDNT, well-differentiated neuroendocrine tumor.

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