We report two clinical cases of primary granulocytic sarcoma of the pancreas that were diagnosed on the surgical specimen. Atypical clinical and morphological presentations may have lead to pretherapeutic biopsies of the pancreatic mass in order to indicate primary chemotherapy. Literature review of this rare clinical presentation may help physicians to anticipate diagnostic and therapeutic strategies

Amielh, David

Chevallier, Caroline

Mariette, Christophe

Messager, Mathieu

English

PubMed

Mathieu Messager

David Amielh

Caroline Chevallier

Christophe Mariette

Springer - Publisher Connector

CASE REPORT Open Access
Isolated granulocytic sarcoma of the pancreas:
A tricky diagnostic for primary pancreatic
extramedullary acute myeloid leukemia
Mathieu Messager1,3, David Amielh1, Caroline Chevallier1,2,3 and Christophe Mariette1,2,3*
Abstract
We report two clinical cases of primary granulocytic sarcoma of the pancreas that were diagnosed on the surgical
specimen. Atypical clinical and morphological presentations may have lead to pretherapeutic biopsies of the
pancreatic mass in order to indicate primary chemotherapy. Literature review of this rare clinical presentation may
help physicians to anticipate diagnostic and therapeutic strategies.
Keywords: Granulocytic sarcoma, Chloroma, Myeloid tumor, Pancreas.
Background
Granulocytic sarcoma (GS) is an extramedullary solid
tumor mass composed of immature myeloid cells [1].
GS is a rare manifestation of acute myeloid leukemia
(AML) usually arising during or after the course of the
disease, in up to 8% of patients in autopsy studies [2].
Occasionally, it can be the first and the only manifesta-
tion of AML, leading to diagnostic challenges. We
report two exceptional cases of isolated pancreatic GS
to focus physicians’ attention to specific diagnostic and
therapeutic strategies for a solid pancreatic mass.
Cases presentation
The first patient was a 45-year-old woman, without signifi-
cant comorbidity, who was referred to our institution for
surgery. Epigastric pain with jaundice began one month
previously without performance status alteration. Standard
blood exams exhibited cholestasis (alkaline phosphatases
3.8 N, gama-glutamyl transpeptidases 37 N) and hyperamy-
lasemia (1.9 N) with normal values of hemoglobin, white
blood cells, platelets, carbohydrate antigen 19-9 (CA19-9)
and carcinoembryonic antigen (CEA). Abdominal com-
puted tomodensitometry (CT scan), magnetic resonance
imaging (MRI) and endoscopic ultrasonography (EUS) of
the pancreas all identified the distension of both the
common bile duct (15 mm) and the Wirsung duct (6 mm),
above a 28 × 20 mm irregular, hypoechoic and hypodense
mass of the pancreatic head, without any lymph node or
vascular invasion or distant secondary lesion detected.
Based on the symptoms, a suspected diagnosis of pancrea-
tic adenocarcinoma and a resectable mass, it was deter-
mined to proceed with primary surgery without obtaining
preoperative sample biopsies. Curative whipple pancreati-
coduodenectomy with regional lymphadenectomy was per-
formed with no specific peroperative discovery and
uneventful postoperative course. Histological examination
of the surgical specimen revealed a pancreatic GS based on
the presence of cells of myeloid lineage with positive
immunostaining for CD43 myeloid-associated antigen
(Figure 1A), whereas immunostainings for other myeloid
markers (CD31, CD34, CD38, CD45, CD99, CD117), B-cell
markers (CD20, CD79a), T-cell markers (CD3, CD4), com-
mune B- and T-cell markers (CD30) and myeloperoxidase
(MPO) were negative. Six weeks later, diffuse relapse
occurred with the appearance of left cervical and multiple
thoracic lymph nodes. After cervical biopsy, histological
analysis confirmed recurrence with the same immunostain-
ing profile. Brain tomodensitometry and bone marrow
biopsy were normal. Cisplatin - cytarabin - dexametha-
sone-based chemotherapy was administered quickly, but
the patient died due to disease dissemination one month
later.
The second patient was a 19-year-old woman, without
significant comorbidity or any alcohol consumption,
* Correspondence: christophe.mariette@chru-lille.fr
1Department of Digestive and Oncological Surgery, Centre Régional et
Universitaire de Lille, Place de Verdun, 59037 Lille cedex, France
Full list of author information is available at the end of the article
Messager et al. World Journal of Surgical Oncology 2012, 10:13
http://www.wjso.com/content/10/1/13 WORLD JOURNAL OF 
SURGICAL ONCOLOGY 
© 2012 Messager et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative
Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
AMPO
CD34
CD43
B
Figure 1 Fixed, paraffin-embedded tissue sections of i) pancreatic invasion (A, case n°1, magnification at ×100) of medium sized cells,
with CD43 positive expression signing myeloid lineage, inset shows contiguous lymph node with high CD43 expression (internal
positive control of myeloid lineage); and of ii) omentum invasion (B, case n°2, hematoxylin and eosin staining, magnification at ×400)
by myeloid-like cells, some with mitotic activity (arrow head), surrounding fat cells (arrow), inserts show myeloperoxydase (MPO),
CD43, and CD34 expression (arrow head showing internal positive control with vessel).
Messager et al. World Journal of Surgical Oncology 2012, 10:13
http://www.wjso.com/content/10/1/13
Page 2 of 5
who presented at our institution for epigastric pains
combined with hyperamylasemia (1.7 N) and hyperlipa-
semia (7.8 N). Hemogram, hepatic enzymes, C-reactive
protein, CEA and Ca 19.9 values were normal. The
abdominal CT scan showed a 9-mm Wirsung duct dila-
tion (Figure 2A) within the 30-mm mass of the pancrea-
tic head (Figure 2B, C), the tumoral or inflammatory
nature of which was uncertain. After conventional medi-
cal treatment for pancreatitis, the symptoms disap-
peared, allowing hospital discharge with additional
morphological outpatient exams scheduled. Due to early
recurrent epigastric pain episodes, combined with hyperli-
pasemia, she was re-admitted. EUS revealed an 11-mm
celiac lymph node with a 9-mm Wirsung duct dilation
and no clear pancreatic mass, whereas pancreatic MRI
identified a moderately low signal intensity on T1-
weighted images, middle-high signal intensity on T2-
weighted images, and minimal enhancement on post-
gadolinium images, consistent with the diagnosis of hypo-
vascular solid tissues. Normal pentetreotide scintigraphy
and the chromogranin A value ruled out the diagnosis of
neuroendocrine tumor. Due to the absence of a clear diag-
nosis, persistent symptoms and the discordance between
the exams that had been performed, the decision was
made to proceed with a surgical exploration, revealing dif-
fuse peritoneal carcinomatosis combined with an unre-
sectable and inflammatory 30-mm pancreatic mass.
Histological analysis of the pancreatic mass and peritoneal
biopsies revealed extramedullar myeloid tumoral cells with
immunohistochemistry positive for MPO, CD43, and
CD34 (Figure 1B), as well as CD117 and CD45, and nega-
tive for CD79a, CD3, CD2, CD4, CD8 and CD68, leading
to the diagnosis of pancreatic GS. The brain CT scan and
bone marrow biopsy were normal. An induction cytara-
bin-based chemotherapy was begun quickly, leading to a
complete morphological response after three consolidation
cycles. Eight months later, left inguinal lymph node recur-
rence was diagnosed. Second-line amsacrine-cytarabin-
based chemotherapy achieved a partial morphological
response. Due to tumoral progression four months later,
third-line clofarabine-based chemotherapy was adminis-
tered with an optimal response that allowed bone marrow
transplantation two months later. Diffuse peritoneal and
hepatic recurrence was diagnosed based on PET scanning
six months later, leading to palliation.
Discussion
GS, also called chloroma, refers to the infrequent green
color observed as a result of myeloperoxydase action in
neoplastic cells [3]. GS usually occurs simultaneously or
follows the onset of AML in 3-10% of patients [1,4].
Rarely, GS is the first manifestation of AML. GS may also
be the first sign of transformation into AML in patients
with myeloproliferative disorders or myelodysplasic syn-
drome [3]. Other common sites of origin are soft tissues,
lymph nodes, skin and bones [5], with abdominal origin
being very rare. Even if GS incidence is increasing due to
prolonged leukemic remission of AML, pancreatic GS
cases have rarely been reported in the literature. To our
knowledge, 10 cases have been published (Table 1)
[4,6-13], only four of which, in addition to the two
reported in the present paper, were isolated pancreatic GS
without bone marrow involvement [6,7,12,13]. Comparing
with other published cases (Table 1), this work is to our
knowledge, the first to describe two isolated pancreatic GS
treated in a single center, with different therapeutic strate-
gies, including a surgical approach. We also provided a
complete follow-up for each case, critically analyzed the
therapeutic strategies and highlighted the wandering diag-
nosis. Regarding other digestive locations, GS of the small
intestine, colon and liver have been described, those situa-
tions being extremely rare [14,15].
GS can occur in patients of all ages with a focus on male
patients (male:female ratio 1.2:1) during the last decades
of life (median age is 56 years, range: 1 month - 89 years)
[7,16]. Even if the overall prognosis of AML is favorable,
the association with GS makes worsens the prognosis
because only 24% of patients with GS will be alive 2 years
after the initial diagnosis, with an overall median survival
of 7 to 20 months [3,17].
A CB
Figure 2 Abdominal computed tomodensitometry, with injection of contrast product, portal sequence. Axial (A) projection showing
Wirsung dilatation (arrow head). Axial (B) and frontal (C) projections showing low density pancreatic mass (arrow heads), case n°2.
Messager et al. World Journal of Surgical Oncology 2012, 10:13
http://www.wjso.com/content/10/1/13
Page 3 of 5
Clinical behavior and response to therapy were not
influenced by any of the following factors: age, sex, ana-
tomic site, de novo presentation, histotype, phenotype
or cytogenetic findings [18]. It remains uncertain what
constitutes the best treatment in GS-associated AML
patients [12]. However, high-dose chemotherapy and
stem cell transplantation may benefit these patients,
whereas radiation therapy or surgical resection have
been found to be less effective [12].
These observations show that clinicians should think
about pancreatic GS when the pancreatic mass develops
during or after AML. However, in the cases reported
here in which GS was the first and the only manifesta-
tion of AML, diagnosis is challenging. Because surgery
is not required and may probably worsen the prognosis
due to the delayed administration of induction che-
motherapy, all efforts should be made to obtain prether-
apeutic biopsies for a pancreatic mass, especially if all of
the biological and morphological exam results are not
typical and in agreement. The negative value of CA19.9
as well as the young age of our patients may have been
warnings that indicate the value of EUS cytological
examination for detecting differential diagnoses of pan-
creatic adenocarcinoma.
A positive diagnosis of GS is sometimes challenging
and requires expert pathologists. Histological observa-
tion reveals myeloblats, promyelocytes and sometimes
neutrophils. The definitive diagnosis of GS requires
positive immunostaining for at least one of the myeloid-
associated antigens (in decreasing frequency: CD68,
MPO, CD43, CD45, CD117, CD99, CD33, CD34, CD13)
associated with negative immunostaining for the lym-
phoid lineages (CD3 for T-cells and CD20 for B-cells)
[1,12]. Major differential diagnoses are Hodgkin lym-
phoma, Burkitt lymphoma, large-cell lymphoma, and
small round cell tumours. When a histological diagnosis
of GS is made, bone marrow sampling is mandatory to
assess the absence of AML.
The risk of metachronous AML occurrence in non-
leukemic patients with GS is very high, with a median
delay of 5 months; most patients will develop AML
within 1 year [7,12]. Therefore, early intensive (induc-
tion/intensification) chemotherapy similar to that used
to treat AML should be administered, even in GS
patients who did not present AML upon initial diagno-
sis [3].
Conclusions
The authors described two cases of isolated granulocytic
sarcoma of the pancreas. The experience of these cases
highlighted the difficulties of correct diagnosis and care.
To conclude, pretherapeutic biopsies should be the cor-
nerstone for the diagnosis of a pancreatic mass with aty-
pical clinical presentation.
Consent
Written informed consent was obtained from the patient
for publication of this case report and the accompanying
images. For the patient who died, consent was sought
from the next of kin of the patient.
Table 1 Clinical characteristics, treatment and outcomes of literature reports of pancreatic granulocytic sarcomas
Author/Year of report Sex
Age
Concomitant
AML
Treatment Response/Status
King et al./1987 F/36 No Radiotherapy + CT (Daunorubicin,
Cytarabine, Thioguanine)
CR
Moreau et al./1996 M/32 No Duodenopancreatectomy + CT
(Idarubin, Cytarabine)
CR after 2 years follow-up
Marcos et al./1997 F/37 Yes None Died after initial MRI
Ravandi - Kashani et al./1999 M/31 Yes CT (Idarubicin, Cytarabine, All-trans
retinoic acid)
CR, (follow-up unknown)
F/61 Yes CT (Idarubicin, Cytarabine, Lisofylline) Recurrence, died
Servin-Abad et al./2003 M/64 In remission CT (Unknown regimen) CR, died of stroke
Breccia et al./2003 F/42 Yes CT (Cytosine, Arabinoside, Idarubicin)+
BM allogarft
CR at 49 months from graft
Schäfer et al./2008 F/75 Yes CT (Etoposide, Cytarabine, reduced
dose Mitoxantrone)
Recurrence (7 months), died
Rong/2010 M/40 No Duodenopancreatectomy + CT
(Cytarabine based regimen)
CR, (follow-up unknown)
Li et al./2011 F/48 No Distal pancreatectomy + splenectomy,
patient refused adjuvant CT
Recurrence (2 months), died 3 months after
surgery
Our study/2011 F/45 No CT after duodenopancreatectomy
(Cisplatin, Aracytine, Dexamethasone)
Early recurrence, died
F/19 No CT (Aracytine based regimen) Recurrence (8 months), alive after BM
transplantation (22 months follow-up)
AML: Acute Myeloid Leukemia; M: Man; F: Female; CT: Chemotherapy; CR: Complete Response; BM: Bone Marrow
Messager et al. World Journal of Surgical Oncology 2012, 10:13
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Page 4 of 5
Acknowledgements
The authors thank Dr. Claire Delattre and Dr. Marion Classe from the
Department of Pathology, University Hospital of Lille, for their help in
collecting and reviewing the histological data.
Author details
1Department of Digestive and Oncological Surgery, Centre Régional et
Universitaire de Lille, Place de Verdun, 59037 Lille cedex, France. 2Université
Lille Nord de France, Place de Verdun, 59045, Lille cedex, France. 3Inserm,
UMR837, Team 5 « Mucins, epithelial differentiation and carcinogenesis »
JPARC, Rue Polonovski, 59045 Lille cedex, France.
Authors’ contributions
Dr. DA and Dr. CC contributed to data collection. Dr. MM and Pr. CM
contributed to writing the manuscript.
Competing interests
The authors declare that they have no competing interests.
Received: 1 November 2011 Accepted: 16 January 2012
Published: 16 January 2012
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Cite this article as: Messager et al.: Isolated granulocytic sarcoma of the
pancreas: A tricky diagnostic for primary pancreatic extramedullary
acute myeloid leukemia. World Journal of Surgical Oncology 2012 10:13.
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Isolated granulocytic sarcoma of the pancreas: A tricky diagnostic for primary pancreatic extramedullary acute myeloid leukemia

International audienceWe report two clinical cases of primary granulocytic sarcoma of the pancreas that were diagnosed on the surgical specimen. Atypical clinical and morphological presentations may have lead to pretherapeutic biopsies of the pancreatic mass in order to indicate primary chemotherapy. Literature review of this rare clinical presentation may help physicians to anticipate diagnostic and therapeutic strategies

HAL-Inserm

Abstract We report two clinical cases of primary granulocytic sarcoma of the pancreas that were diagnosed on the surgical specimen. Atypical clinical and morphological presentations may have lead to pretherapeutic biopsies of the pancreatic mass in order to indicate primary chemotherapy. Literature review of this rare clinical presentation may help physicians to anticipate diagnostic and therapeutic strategies.</p

Messager Mathieu

Amielh David

Chevallier Caroline

Mariette Christophe

Directory of Open Access Journals

World Journal of Surgical Oncology

Abstract
          We report two clinical cases of primary granulocytic sarcoma of the pancreas that were diagnosed on the surgical specimen. Atypical clinical and morphological presentations may have lead to pretherapeutic biopsies of the pancreatic mass in order to indicate primary chemotherapy. Literature review of this rare clinical presentation may help physicians to anticipate diagnostic and therapeutic strategies.</jats:p

Crossref

AA: Obstructive jaundice. An unusual presentation of granulocytic sarcoma. Cancer

Abdominal granulocytic sarcomas: demonstration by MRI. Magn Reson Imaging

Alimena G: Clinico-pathological characteristics of myeloid sarcoma at diagnosis and during follow-up: report of 12 cases from a single institution. Leuk Res

Alimena G: Granulocytic sarcoma of the pancreas successfully treated with intensive chemotherapy and stem cell transplantation.

Buyukberber NM: Granulocytic sarcoma of the colon and leukemic infiltration of the liver in a patient presenting with hematochezia and jaundice. Digestion

DT: Myeloid sarcoma of the small bowel associated with a CBFbeta/MYH11 fusion and inv(16)(p13q22): a case report.

Extramedullary myeloid cell tumors in acute nonlymphocytic leukemia: a clinical review.

Fan YZ: Isolated pancreatic granulocytic sarcoma: a case report and review of the literature.

FJ: Granulocytic sarcoma of the pancreas: a report of two cases and literature review. Clin Lab Haematol

Granulocytic sarcoma of Core-binding Factor (CBF) acute myeloid leukemia mimicking pancreatic cancer. Leuk Res

Granulocytic sarcoma of the pancreas: a case report and review of the literatures.

Granulocytic sarcoma of the pancreas. A report of one case and review of the literature. Acta Haematol

Harousseau JL: Primary granulocytic sarcoma of the pancreas: efficacy of early treatment with intensive chemotherapy. Rev Med Interne

JM: Granulocytic sarcoma: a clinicopathologic study of 61 biopsied cases. Cancer

Myeloid sarcoma: clinico-pathologic, phenotypic and cytogenetic analysis of 92 adult patients. Leukemia

Shiku H: Granulocytic sarcoma of mesentery in acute myeloid leukemia with CBFB/MYH11 fusion gene but not inv(16) chromosome: case report and review of literature. Leuk Res

Sidhu-Malik N: Granulocytic sarcoma in the absence of myeloid leukemia.

Vardiman JW: WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues.

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Isolated granulocytic sarcoma of the pancreas: A tricky diagnostic for primary pancreatic extramedullary acute myeloid leukemia

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