1. ACTA CYTOLOGICA 2012;56:325-329
DYSPLASTIC MEGAKARYOCYTES AND
EOSINOPHILIC PRECURSORS IN THE
DIAGNOSIS OF MYELOID SARCOMA ON LYMPH
NODE FINE-NEEDLE ASPIRATION CYTOLOGY
Dr. Saurav Singh

2. INTRODUCTION

Myeloid sarcoma is a rare manifestation characterized by the
occurrence of 1 or more tumorous myeloid masses at an
extramedullary site.

It is also known as extramedullary acute myeloid leukemia
(AML), extramedullary myeloid tumor, myeloblastoma,
granulocytic sarcoma or chloroma.

3. 
Myeloid precursors on fine-needle aspiration can be seen in a
variety of pathological states, both neoplastic and nonneoplastic.

Myeloid sarcoma can precede, occur concurrently, or arise
subsequent to the diagnosis of AML.

It can also arise in patients with myelodysplastic syndrome,
chronic myeloproliferative disease and myelodysplastic
disease.

The incidence of myeloid sarcoma ranges from 1 to 3%.

4. 
The most common sites of myeloid sarcoma are the
subperiosteal bone structures of the skull, paranasal sinuses,
bones, lymph nodes, and skin.

Less common sites are central nervous system, spinal cord,
breast, heart, thymus, liver, spleen, pancreas, endocrine
glands and female genital tracts.

5. 
1)
2)
3)
Myeloid sarcoma occurs in patients with AML in three clinical
settings:
Most often, myeloid sarcoma is associated with concurrent
evidence of AML involving the blood and bone marrow.
Myeloid sarcoma can arise in patients with a history of AML
as a sign of relapse.
Least frequently, myeloid sarcoma can arise in patients
without a history or concurrent evidence of AML.

6. 
Myeloid sarcoma can show unilineage or multilineage
proliferation and is further sub classified within the WHO
scheme as differentiated, immature, and blastic.

Differentiated tumors are composed of numerous
promyelocytes and more mature granulocytic cells.

Immature
tumors
are
composed
of
myeloblasts,
promyelocyte and blastic tumors which is least mature.

They are composed predominantly of myeloblasts with little
evidence of granulocytic differentiation.

7. 
Proliferation of the erythroid or megakaryocytic series can also
be seen in myeloid sarcoma, most often in cases with chronic
myeloproliferative disease or myelodysplastic syndrome.

Megakaryocytes may be dysplastic, small or abnormally large
in size with hyper or hypolobated nuclei, or show
hyperchromasia.

Thus, the presence of immature myeloid cells, eosinophilic
precursors or dysplastic megakaryocytes is supportive of the
neoplastic nature of a myeloid proliferation.

8. MATERIALS AND METHODS

During the course of study nearly 4186 FNAC of lymph nodes
were performed.

186 were diagnosed as hematolymphoid malignancies of
which 15 cases were diagnosed as myeloid sarcoma with the
involvement of lymph node in 10 cases.

FNAC was performed using 23- gauge disposable needle and
10 ml disposable syringe. Both non-aspiration and aspiration
techniques were used.

Peripheral smears of all cases were made by using finger
prick technique and stained with Giemsa stain.

9. RESULTS

The differentiation of granulocytic sarcoma from malignant
lymphomas and other small round cell tumors is very critical.

11. 

Location of Extramedullary Proliferation:
In this, 7 patients presented with multiple lymphadenopathy
and 3 patients with enlargement of a single group of lymph
nodes.

The majority of the patients (8 cases) presented with cervical
lymphadenopathy and 6 of these also showed inguinal and
axillary lymphadenopathy.

One case had isolated inguinal lymphadenopathy and the
other had multiple lymph nodes involving inguinal, axillary,
pre and para -aortic groups.

12. CLINICAL PRESENTATION

Four patients were less than 20 years of age,3 were in the
age group of 21-40, 2 were between 41 and 60 and 1 was
more than 60 years of age.

The male: female ratio was 2:1.

Six patient had fever at the time of presentation,4 had
hepatosplenomegaly of moderate grade,4 had symptoms
related to anemia, 1 patient had skin lesions and 1 had gum
bleeding.

Pre- FNAC diagnosis of a neoplastic process was present in
only 2 cases (1 case of AML and 1 of CML).

In all other cases, diagnosis was confirmed by examination of
peripheral smear, bone marrow examination, flow cytometry or
cytogenetics.

13. LABORATORY FINDINGS

Complete Blood count and Peripheral Blood Smear

Total white blood cell count was raised in 8 cases, normal in 1
case and decreased in 1 case.
Peripheral blood smears of all patients were taken and
stained with Giemsa stain.
Eight cases showed the presence of blasts or myeloid
precursors in the peripheral blood.
Three of the 8 cases showed an AML –like picture with blasts>
20% and 4 cases showed features of CMPD with immature
myeloid precursors, eosinophils and eosinophilic precursors,
occasional basophils and blasts < 10%.
One case showed atypical monocytoid cells without
cytoplasmic granularity on PBS.





14. FNAC FINDINGS:

1.
2.
3.
Cytological findings that suggested the diagnosis were:
The presence of immature myeloid series cells, especially
eosinophilic precursors.
Blasts with cytoplasmic granularity.
Dysplastic megakaryocytes.

19. 
Megakaryocytes with dysplastic forms were seen in 5 of the10
cases(2 CML, 1 AML and 2 cases where PBS do not show
blast) and in conjugation with eosinophilic precursors helped
in the diagnosis of myeloid sarcoma.

20. FOLLOW- UP

In this study, there were 10 patients where myeloid precursors
were seen on fine- needle aspiration of lymph nodes and were
diagnosed as myeloid sarcoma.

On further investigations, 3 cases were diagnosed as CML on
PBS.

1 case was diagnosed as juvenile myelomonocytic leukemia,
as the LAP(leukocyte alkaline phosphatase) score was 18
(normal range 20-180) and the Philadelphia chromosome was
negative; 2 cases did not show lasts on PBS, however one of
them was diagnosed as MPD on bone marrow aspirate.

21. DISCUSSION

Myeloid sarcoma of the lymph node is an uncommon entity
and should be distinguished from myeloid metaplasia and
Non- Hodgkin lymphoma.

Extramedullary hematopoiesis (EMH) or myeloid metaplasia
can occur in the lymph nodes of children with benign
hematological disorders like:
Thalassemia
Hereditary spherocytosis
Sickle cell anemia
Congenital dys-erythroblastic anemia
Immature thrombocytopenic purpura






22. 
Extramedullary hematopoiesis can show either unilineage or
multineage proliferation like myeloid sarcoma.

The presence of myeloid precursors including blasts,
eosinophilic precursors and dysplastic megakaryocytes is not
seen with extramedullary hematopoiesis.

This favors a diagnosis of
extramedullary hematopoiesis.
myeloid
sarcoma
over

23. 
Myeloid sarcoma can closely resemble diffuse large cell
lymphomas of B cell or T cell lineage and without clinical
history and high index of suspicion are likely to be
misdiagnosed.

Cytologically, diffuse large B cell lymphoma have one or more
prominent nucleoli and thick nuclear membranes.

Myeloid sarcomas have eosinophilic myelocytes or other
myeloid precursors which differentiate it from non-Hodgkin
lymphoma.

Blasts in myeloid sarcoma also show cytoplasmic granularity
which is absent in non- Hodgkin lymphoma.

24. 
In the study, 1 case which showed atypical monocytoid cells
and eosinophilic precursors on FNAC was diagnosed on flow
cytometry as pre-T ALL.

Pre-T ALL is usually infiltrated by eosinophils and some of
these cases have developed AML, MDS or myeloid sarcoma,
suggesting that both neoplasm arise from common progenitor
cell.

25. 
Two cases had a normal PBS, but the presence of
eosinophilic precursors and dysplatic megakaryocytes in both
of them favors a diagnosis of myeloid sarcoma over
extramedullay hematopoiesis.

However, myeloid sarcoma can precede diagnosis of AML or
other MPD.

26. 
Thus, the presence of eosinophilic myeloid precursors and
dysplastic megakaryocytes in aspirates should suggest a
diagnosis of myeloid sarcoma, even in the absence of a
documented myeloproliferative disease.

27. ACTA CYTOLOGICA 2012;56:228-232
FINE NEEDLE ASPIRATE OF AUTOIMMUNE
PANCREATITIS
(LYMPHOPLASMACYTIC
SCLEROSING PANCREATITIS):
CYTOMORPHOLOGIC CHARACTERISTICS AND
CLINICAL CORRELATES

28. INTRODUCTION

Autoimmune pancreatitis (AIP) is an inflammatory disease of
the
pancreas
characterized
by
a
duct-centric
lymphoplasmacytic infiltrate and fibrosis.

It is a benign condition that is often treated by nonsurgical
methods such as corticosteroid therapy.

Patients with autoimmune pancreatitis have elevated level of
serum IgG4 which can aid in the preoperative diagnosis of the
disease.

29. 
AIP commonly presents with obstructive jaundice or weight
loss.

It can form a mass-like lesion in the head of the pancreas.

AIP and ductal adenocarcinoma is challenging in the absence
of a tissue diagnosis.

30. MATERIALS AND METHODS

•
•
Case Selection:
The search criteria ‘autoimmune pancreatitis’ and ‘
lymphoplasmacytic sclerosing pancreatitis’ were used to
identify surgical pancreatic specimens.
Following clinical and pathologic data were collected for each
case.
Age, gender, ethinicity, presenting symptoms , date and
results of preoperative imaging studies, including radiographic
impression of a mass and biliary cytology.

31. CYTOPATHOLOGY

Material was obtained by transabdominal ultrasound or
endoscopic ultrasound-guided FNA.

Direct smears were prepared and stained with Diff Quick as
well as wet-fixed for Papanicolaou staining.

The cytologic criteria used to define ductal atypia included the
presence of nuclear abnormalities such as:
Hyperchromasia
Irregular nuclear borders
An increased nuclear-to-cytoplasmic ratio
Architectural abnormalities such as the presence of
disorganization within tissue fragments.





32. SURGICAL PATHOLOGY

Specimens were processed using standard methods and
stained with hematoxylin and eosin.

Based on the diagnosis determined at the time of original
evaluation, the surgical and cytopathologic data were
collected.

The results of IgG4 immunolabeling were available for 10
surgical cases.

33. 
IgG4 immunolabeling was performed on a Ventana XT
benchmark automated stainer.

Antigen retrieval was done using enzyme Protease 1 for 8
min.

Incubation with mouse anti-human IgG4 was performed for 8
min at room temperature followed by an amplification step.

34. 
Hematoxylin counterstain was applied to all sections before
dehydration.

A surgical specimen was determined to have increased IgG4–
positive plasma cells if > 10 IgG4- positive cells were present
per high power field.

35. RESULTS

A total of 20 FNAs from 17 patients were identified.

37. 
Fifteen patients were diagnosed with AIP based
examination of a surgical resection specimen.
on

Two were diagnosed by a combination of clinical history.

The surgical resections included eight Whipple resections,
four distal pancreatectomies, four surgical biopsies and one
Frey procedure.

39. 
Of the 10 aspirates diagnosed as atypical ,the majority were
described as having rare, focal, or scattered atypical ductal
cells while 1 was suspicious for malignancy, 1 could not
exclude a neuroendocrine neoplasm, and 1 was makedly
atypical.

40. 
Common findings included hypocellularity with a smear
background lacking red blood cells.

Rare, oval-shaped fibroblastic nuclei or fragments of fibrous
tissue were identified.

41. 
Seven of the 20 pancreatic FNA were accompanied by
separate biliary cytology.

Of these specimens, one was diagnosed as markedly atypical
and suspicious for malignancy.

IHC labeling for IgG4 was performed on the surgical
specimens.

9 out of 10 cases demonstrating increased numbers of IgG4positive plasma cells.

51. DISCUSSION

AIP is defined as a mixed inflammatory cell infiltrate centered on
the pancreatic ducts with an associated venulitis.

It is important to distinguish between pancreatic ductal carcinoma
and AIP since they have overlapping clinical and radiological
features.

The most common cytomorphological findings of AIP included
cellular stromal fragments and inflammatory cells, present either
within the stroma or in the background.

In this study, pancreatic FNA of AIP most frequently led to an
‘atypical’ cytopathologic interpretation.

The presence of significant epithelial atypia was often limited to a
few or scattered groups of ductal cells.

This is due to the surrounding inflammatory and fibrotic process.

52. 
In the cases available for review ,the most common findings
were hypocellular background lacking red blood cells.

Fragments of fibrous tissue and focally atypical ductal
epithelium were frequently seen.

Inflammatory cells were not observed in majority of cases.

53. 








AIP is considered one of several manifestations of systemic
IgG4- related disease.
They may affect diverse organs including:
Bile duct
Salivary gland
Lacrimal gland
Retroperitoneum
Aorta
Lung
Kidney

54. 
Extrapancreatic
manifestations,
including
sclerosing
cholangitis, appear to be more commonly associated with the
lobulocentric pattern of AIP.

Also, majority of the accompanying biliary cytology specimens
were found to be benign.

Elevation of serum IgG4 is invariably associated with AIP, thus
immunolabeling for IgG-positive plasma cells on histologic
sections has become a key diagnostic tool.

55. 
Based on the result of the present study, this ancillary
technique may prove most useful in cases with worrisome but
inconclusive atypia or scant cytologic material.

In such cases performing IgG4 immunolabeling on the cell
block material may demonstrate elevated IgG4 – positive
plasma cells, providing an important clue to correct diagnosis
and altering the patient’s treatment course.