1) The document discusses the cytological findings of fine needle aspiration of lymph nodes in cases of myeloid sarcoma and autoimmune pancreatitis. In myeloid sarcoma, the presence of immature myeloid cells, eosinophilic precursors, and dysplastic megakaryocytes supports the diagnosis. In autoimmune pancreatitis, common findings include hypocellular smears with rare atypical ductal cells and fragments of fibrous tissue. 2) Distinguishing these conditions from other entities such as lymphoma and pancreatic cancer is important but can be challenging based on cytology alone. Immunostaining for IgG4+ plasma cells is useful in diagnosing autoimmune pancreatitis. 3) The document

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.