[Rare Tumors 2012; 4:e36][page 115]
Jitendra Singh Nigam, Vatsala Misra,
College, Allahabad, India
ment, swelling over both legs and breathless-
ness for three month. On clinical examination
diagnosis of fibroadenoma breast was made.
Ultrasonography of abdomen showed bilateral
ovarian mass. Bilateral salpingo-ophrectomy
was done and specimen was sent for histologi-
cal examination. Two lobulated solid masses of
tissues the larger one measuring 13¥8¥5 cm
and smaller one measuring 10¥7¥5 cm in size
received. Microscopic examination showed
monomorphic population of discohesive,
hyperchromatic small round cells had high N:C
ratio, coarse chromatin, conspicuous nucleoli
and scant to moderate amount of basophilic
cytoplasm, lying in sheets and separated by
fibrous strands and diffusely infiltrating the
ovarian stroma. Fine needle aspiration from
breast lump and leg swelling showed predomi-
nant population of blast cells. Myeloperoxidase
was strongly positive and diagnosis of granulo-
cytic sarcoma was confirmed.
sarcoma presenting at multiple
Varsha Kumar, Kachnar Varma
sites: ovary, breast and
Department of Pathology, M.L.N. Medical
An 18 year old female presented with the
history of pain in abdomen, breast engorge-
dominantly of cells showing granulocytic differ-
entiation (granulocytic sarcoma) or predomi-
nantly of cells showing monocytic differentia-
tion (monocytic sarcoma).1It occurs in 2 to 14%
of cases of acute myeloid leukemia (AML).2The
tumors may occur as extramedullary masses
without evidence of leukemia in blood or mar-
row, so-called nonleukemic granulocytic sarco-
mas, or in association with AML. The tumors
originally were called chloromas because of the
green color imparted by the high concentration
of the enzyme myeloperoxidase present in
myelogenous leukemic cells. Biopsy specimens
are positive for chloracetate esterase, lysozyme,
myeloperoxidase, and cluster of differentiation
(CD) markers of myeloid cells.3The tumors are
usually localized; they often involve bone,
periosteum, soft tissues, lymph nodes, or skin.
Granulocytic sarcomas are solid extra -
medullary tumors that can be composed pre-
Common sites are the orbit and the paranasal
sinuses, but other sites reported include the
gastrointestinal tract, genitourinary tract,
breast, cervix, salivary glands, mediastinum,
pleura, peritoneum, and bile duct. Granulocytic
sarcomas may occur at diagnosis of AML or may
precede the diagnosis; they have also been seen
in association with myelodysplastic syndromes
or myeloproliferative disorders and usually pre-
dict transformation to acute leukaemia.2
Patients with granulocytic sarcoma have a poor
prognosis and the majority of patients without
bone marrow infiltration at presentation die of
leukemia within an average of 16.5 months
after diagnosis.4,5Granulocytic sarcoma of the
breast is an unusual site of presentation occur-
ring mainly in young women, with high inci-
dence of bilaterality.4-8The ovary contains tumor
in approximately 25% of patients with non-
Hodgkin’s lymphoma at autopsy and in up to
50% of those with leukemia. However, with the
exception of Burkitt lymphoma, ovarian involve-
ment as the initial manifestation of lymphoma
or leukemia is rare.9
engorgement, swelling over both legs and
breathlessness for three months. Clinical
examination revealed bilateral breast masses.
A clinical diagnosis of fibroadenoma breast
was made. Bilateral ovarian mass were seen
on ultrasonography of abdomen. Total leuco-
cyte count was within normal limits. No blasts
cells were identified in the peripheral blood
smear. Bilateral salpingo-ophrectomy was
done and specimen was sent for histological
An eighteen year old female presented with
the history of pain in abdomen, breast
Outer surface was encapsulated and cut sur-
face of both the masses was tan grey with mul-
tiple small hemorrhagic and brownish areas
(Figure 1A, B). Several pieces from different
areas including center and outer surface were
processed from both masses.
Two lobulated solid masses of tissues the
larger one measuring 13¥8¥5 cm and smaller
one measuring 10¥7¥5 cm in size received.
cohesive, lying in sheets and separated by
fibrous strands of variable thickness. Cells were
hyperchromatic, had high nuclear cytoplasmic
ratio, coarse chromatin, conspicuous nucleoli
and scant to moderate amount of basophilic
Sections processed showed monomorphic
population of small round cells diffusely infil-
trating the ovarian stroma. These cells were dis-
cytoplasm. One-two mitotic figures per high
power field were noted. One section showed
large corpus luteumof ovary with central area of
hemorrhage (Figures 1C-E and 2A,B).
Fine needle aspiration from breast lump and
leg swelling were also done. Fine needle aspi-
ration smears prepared showed predominant
population of large round to oval cells with
moderately high nuclear cytoplasmic ratio and
moderate amount of pale blue cytoplasm.
Nuclei were round to oval with two to four
prominent nucleoli (blast cells). Few large
monocytoid cells with prominent nucleoli were
also seen (Figures 2C-E).
A diagnosis of small round cell tumor of
ovary with differential
Granulocytic sarcoma, Lymphoma, Small cell
carcinoma and juvenile granulosa cell tumor
Immunohistochemistry for myeloperoxi-
dase, LCA (CD45), CD 34, and placental alka-
line phosphatase was done. It was strongly pos-
itive for myeloperoxidase. Rest three were
negative (Figures 3A-D). A diagnosis of granu-
locytic sarcoma was confirmed.
A repeat peripheral blood smear examines
but this time these smear showed normal total
leukocyte count with occasional blast cells
(Figure 2F). Patient was referred to oncology
center for treatment. She did not report back to
our center and lost to follow up.
Approximately half of the tumors are bilateral.9
Primary involvement of the ovary is exceeding-
ly rare leading to under diagnosis of granulo-
Ovarian involvement as the initial manifes-
tation of lymphoma or leukemia is rare.
Rare Tumors 2012; volume 4:e36
Department of Pathology, M.L.N. Medical College,
Allahabad, India. Tel. +91.941.262.8083.
Key words: breast lump, myeloblast, ovarian
mass, soft tissue.
Conflict of interests: the authors report no poten-
tial conflict of interests.
Received for publication: 25 February 2012.
Accepted for publication: 5 March 2012.
This work is licensed under a Creative Commons
Attribution NonCommercial 3.0 License (CC BY-
©Copyright J.S. Nigam et al., 2012
Licensee PAGEPress, Italy
Rare Tumors 2012; 4:e36
[page 116][Rare Tumors 2012; 4:e36]
cytic sarcoma.10It can arise de novo and pre-
cede the development of acute nonlymphocytic
leukemia, or be the sole manifestation of
In granulocytic sarcoma of the breast the
patients mainly present with the breast
engorgement and a painless mass without
associated local symptoms.6
In granulocytic sarcoma ovary both diffuse
and nodular growth patterns are encountered,
but sclerosis can distort these patterns and
result in compartmentalization of the neoplas-
tic cells, as well as growth as nests and cords.
The single-file arrangement of lymphoma and
leukemic cells may simulate metastatic carci-
noma, particularly one of breast origin.
Granulocytic sarcoma on routine stains is
often composed of cells with more finely dis-
persed nuclear chromatin and may have more
abundant cytoplasm, which may be deeply
eosinophilic. Confirmatory immunostaining
may be crucial in making the diagnosis.9
In granulocytic sarcoma the growth pattern
may simulate invasive lobular carcinoma or
malignant lymphoma. The neoplastic cells
forming broad sheets or cords invade into and
around normal mammary parenchymal struc-
tures. Intra-epithelial extension of the
leukemic infiltrate simulates in situ carcino-
ma. The diagnosis of granulocytic sarcoma
may be suggested by cytoplasmic granules in
maturing myeloid cells or by the presence of
relatively numerous mature myeloid cells scat-
tered throughout the lesion. Special stains are
especially helpful to establish the diagnosis.
The tumor cells do not contain mucin and they
give a negative reaction for immunocytochem-
ical epithelial markers such as cytokeratin and
anti-endomysial antibodies. The diagnosis of
granulocytic sarcoma can be established by
fine needle aspiration biopsy if immature mye-
locytic cells are recognized in the cytologic
The differential diagnosis
includes non-Hodgkin lymphoma (predomi-
nantly mucosa-associated lymphoid tissue lym-
phoma and diffuse large B-cell lymphoma),
small round cell tumors, granulosa cell tumor,
undifferentiated carcinoma and in case of
breast, lobular carcinoma also.12A complete
panel of immunohistochemistry is helpful to
recognize this entity with an isolated presenta-
tion. Granulocytic sarcoma is immunoreactive
for myeloperoxidase, CD117 and CD68, CD43
is positive in most of the cases, and 75% are
reactive for CD45. Lysozyme and CD68 PGM1
expression are evidence for monocytic differ-
entiation.13,14Multiple sites involvement in sin-
gle patient was reported in literature.6,15-20In
the presented case multiple sites (both
ovaries, both breasts, and leg swelling) were
involved. Due to the rarity of isolated granulo-
cytic sarcoma and different treatments, the
clinical outcome and the prognosis in this
group of patients is poor.
Figure 2. A) Large proliferating blood vessel surrounded by monomorphic population of
small round cells (Hematoxylin & Eosin 100¥); B) hyperchromatic small round cells had
high N:C ratio, coarse chromatin and scant to moderate amount of basophilic cytoplasm
(Hematoxylin & Eosin 100¥); C) Fine needle aspiration (FNA) left breast: large round to
oval cells with high nuclear cytoplasmic ratio and 2 to 4 nucleoli (Giemsa 1000¥); D) FNA
right breast: large round to oval cells with high nuclear cytoplasmic ratio and 2 to 4 nucle-
oli (Giemsa 1000¥); E) FNA leg swelling: large round to oval cells with high nuclear cyto-
plasmic ratio and 2 to 4 nucleoli (Giemsa 1000¥); F) peripheral blood smear: large round
to oval cells with high nuclear cytoplasmic ratio and 2 to 4 nucleoli (Giemsa 1000¥).
Figure 1. A) Gross: lobulated solid mass of ovary; B) cut surface of masses was tan grey
with raised lobulated areas; C) monomorphic population of small round cells diffusely
infiltrating the ovarian stroma with large corpus luteum of ovary, (arrow; Hematoxylin &
Eosin 100¥); D) monomorphic population of small round cells infiltrating the capsular
(Hematoxylin & Eosin 100¥); E) monomorphic population of small round cells diffuse-
ly infiltrating the ovarian stroma adjescent to leuteal cells (arrow, Hematoxylin & Eosin
100¥); F) proliferating blood vessels and diffuse infiltration of hyperchromatic small
round cells with high N:C ratio (Hematoxylin & Eosin 400¥).
[Rare Tumors 2012; 4:e36] [page 117]
tion without development of leukemia or
myeloproliferative disorder is extremely rare.
Immunohistochemistry and Ancillary studies
are necessary to recognize this entity.
Granulocytic sarcoma is uncommon in ovary
and breast neoplasm and the clinical presenta-
2. Baer MR, Greer JP. Acute myeloid
leukaemia in adults. In: Greer JP, Foerster
J, Rodgers GM, et al. Wintrobe’s Clinical
Haematology, 12th Edition. Philadelphia:
Lippincott Williams & Wilkins; 2009. pp
3. Kaushansky K, Lichtman MA, Kipps TJ, et
al. Williams Haematology, 8th edition.
China: The McGraw-Hill Companies; 2010.
4. Gartenhaus WS, Mir R, Pliskin A, et al.
1. Barbara J. Bain. Leukaemia diagnosis, 4th
edition. Singapore: Wiley-Blackwell; 2010.
Granulocytic sarcoma of the breast:
aleukemic bilateral metachronous presen-
tation and literature review. Med Pediatr
5. Paydas S, Zorludemir S, Ergin M.
Granulocytic sarcoma: 32 cases and review
of the literature. Leuk Lymphoma 2006;47:
6. Valbuena JR, Admirand JH, Gualco G,
Madeiros LJ. Myeloid sarcoma involving
the breast. Arch Pathol Lab Med 2005;129:
7. Cassi E, Tosi A, De PA, et al. Granulocytic
sarcoma without evidence of acute
leukaemia: 2 cases with unusual localiza-
tion (uterus and breast) and one case with
bone localization. Haematologica 1984;
8. Vela-Chávez TA, Arrecillas-Zamora MD,
Quintero-Cuadra LY, Fend F. Granulocytic
sarcoma of the breast without develop-
ment of bone marrow involvement: a case
report. Diagn Pathol 2009;4:2
9. Young RH, Clement PB. Miscellaneous pri-
mary tumours, secondary tumours, and
nonneoplastic lesions of the ovary. In:
Mills SE. Sternberg’s diagnostic surgical
pathology, 5th Edition. Philadelphia:
Lippincott Williams & Wilkins; 2010. pp
10. Mehta J, Kane S. Primary granulocytic sar-
coma of ovary a rare presentation. Leuk
11. Sreejith G, Gangadharan VP, Elizabath KA,
et al. Primary granulocytic sarcoma of the
ovary. Am J Clin Oncol 2000;23:239-40.
12. Rosen PP. Rosen’s breast pathology, 3rd
Edition. Philadelphia: Lippincott Williams
& Wilkins; 2010.
13. Chen J, Yanuck RR, Abbondanzo SL, et al.
c-Kit (CD 117) reactivity in extramedullary
myeloid tumour/granulocytic sarcoma.
Arch Pathol Lab Med 2001;125:1448-52.
14. Traweek ST, Arber DA, Rappaport H,
Brynes RK. Extramedullary myeloid cell
tumours. An immunohistochemical and
morphologic study of 28 cases. Am J Surg
15. Tsikitis VL, Corning C, Henderson J, Rose
J. Chloroma/granulocytic sarcoma abdomi-
nal and pelvic presentation of acute myel-
ogenous leukaemia. J Cancer 2010;1:98-
16. Park HJ, Jeong DH, Song HG, et al. Myeloid
sarcoma of both kidneys, the brain, and
multiple bones in a nonleukemic child.
Yenisei Med J 2003;44:740-3.
17. Makis W, Hickeson M, Derbekyan V.
Myeloid sarcoma presenting as an anteri-
or mediastinal mass invading the peri-
cardium: Serial Imaging With F-18 FDG
PET/CT. Clin Nucl Med 2010;35:706-9.
18. Al-Quran SZ, Olivares A, Lin P, et al.
Myeloid sarcoma of the urinary bladder
and epididymis as a primary manifestation
of acute myeloid leukaemia with inv(16).
Arch Pathol Lab Med 2006;130:862-6.
19. Kilic G, Boruban MC, Bueco-Ramos C,
Konoplev SN. Granulocytic sarcoma involv-
ing the uterus and right fallopian tube
with negative endometrial biopsy. Eur J
Gynaecol Oncol 2007;28:270-2.
20. Garcia MG, Deavers MT, Knoblock RJ, et al.
Myeloid sarcoma involving the gynaeco-
logic tract: a report of 11 cases and review
of the literature. Am J Clin Pathol 2006;
Figure 3. Immunohistochemistry: A) myeloperoxidase strongly positive in tumor cells
(400¥); B) LCA (CD45) was negative in tumor cells, infiltrating normal lymphocytes are
positive (400¥); C) placental alkaline phosphatase is negative in tumor cells (400¥); D)
vimentin is negative in tumor cells (400¥).