7. 4) variations in pancreaticobiliary anatomy
5)Age : elderly
6)Sex : male:female—1.6:1
CLINICAL FEATURES
Characteristic painless obstructive jaundice
Pruritus, dark urine, pale stools, steatorrhea
If no jaundice, symptoms are vague e.g. discomfort,
anorexia, weight loss
Peripheral venous thrombi & diabetes
9. LOCATION & GROSS FEATURES
2/3 rd – head of the pancreas
1/3 rd – body & tail of pancreas
Multiple tumours in 20 % of cases
GROSSLY,
- poorly delineated, firm
- yellowish grey cut surface
- rarely massive cystic degeneration
- pancreatic ducts- dilated and plugged with
necrotic tumour
- extrapancreatic extension is common
10. Gross appearance of typical invasive ductal carcinoma of the head of
the pancreas. The tumor is protruding into the duodenal lumen.
11. MICROSCOPIC FEATURES
Grading- well/moderately/ poorly defferentiated
Low power view-
well formed glands, with large lumen, lined
by one or few layers of cylindrical or cuboidal
epithelium.
irregularities in shape & distribution of
glands, prominent concentric desmoplastic
stroma surrounding the glands.
13. High power view : epithelium show malignant
features i.e. marked nuclear pleomorphism, loss of
polarity, prominent nucleoli & mitotic activity
Disparity between high degree of cytologic atypia
And low level of archirectural atypia.
Invasion : Perineural invasion, invasion of veins,
fat invasion
Carcinoma in situ( high grade pancreatic intra
epithelial neoplasm) & atypical hyperplasia
Lobular tissue destroyed, islet cell preserved –
“insular pancreas”
14. Pancreatic ductal adenocarcinoma.:It is typical of this tumor type to be
well differentiated architecturally but to show marked cytologic atypia
19. MOLECULAR GENETIC FEATURES
Structural rearrangements or loss of genes on 1p,
3p, 6p, 8p & 17 p
Mutations of K-RAS
Inactivating mutations of P16/CDKN2A
Mutations of TP 53
Inactivating mutations of DPC 4 (strongly
suggestive)
Overexpression of HER2
Loss or overexpression of DNA mismatch repair
genes
22. SPREAD AND METASTASIS
Peri pancreatic soft tissue
Invasion into the duodenum & common bile duct
Vascular & neural invasion
Lymphnode metastais
Distant metastasis
TREATMENT
PRIMARILY SURGICAL
23. PROGNOSIS
Overall 5 year survival rate is 4 % or less
Mean survival of 3 months
Factors related to prognosis are :
Tumour stage
microscopic grade
Tumor size
Tumour less than 4.5 cm in diameter– longest survival
Blood vessel invasion & retroperitoneal margin of
resection—decreased survival
Lymphnode metastasis
24. DNA ploidy
TGF- β1 expression– related to better differentiated
tumours—better outcome
Cytokeratin 20 expression—decreased survival
Mapsin expression—better prognosis
SMAD4 gene mutation—worse prognosis
25. ANAPLASTIC CARCINOMA
Also known as PLEOMORPHIC, SARCOMATOID
OR UNDIFFERENTIATED CARCINOMA
Highly distinctive morphology and highly aggressive
course
> 50 years, male predilection
Three morphologic types:
1)
Large no. of bizzare multinucleated cells
Poor cellular cohesion(loss of E-cadherin expression)
Lymphnode & hematogenous metastasis common
26. 2) tumour largly composed of spindle shaped cells
3)solid tumour of small monotonous round cells
Immunohistochemically, keratin, EMA & CEA
positive
Prognosis : extremely poor
27. Sarcomatoid carcinoma of the pancreas associated with areas of clear-
cut glandular differentiation. The two components are sharply separated,
resulting in a carcinosarcoma-type appearance.
28. GIANT CELL TUMOUR OF PANCREAS
Distinct morphologic appearance and better
prognosis
Grossly, large and hemorrhagic
Microscopically, dual polulation :
Uniform spindle cells of mesenchymal origin with
cytological atypia
Multinucleated giant cells (=osteoclasts)
Nuclei of osteoclast like cells are uniform small and
mitoses and bizarre forms are absent.
29. Gross appearance of giant cell tumor of pancreas. There is a large
hemorrhagic mass in the head of the pancreas that is protruding into
the stomach.
30. Microscopic appearance of giant cell tumor of the pancreas. Osteoclast-like
multinucleated giant cells are seen scattered among mononuclear
neoplastic elements showing a high degree of atypia
31. CYSTIC PANCREATIC NEOPLASMS
Tumours in which cystic configuration is universally
present and part of their definition(i.e.
cystadenoma & cystadenocarcinoma)
Two distinct categories : microcystic and mucinous
MICROCYSTIC CYSTADENOMA
Also known as glycogen rich or serous
cystadenoma.
Usually in elderly
Some cases aassociated with VHL gene mutations
32. A and B, Microcystic adenoma of pancreas.
A, The tumor, which is sharply outlined, shows numerous small cysts.
B, Close-up of another case showing innumerable cystic cavities
separated by a thin fibrous wall.
33. Grossly, large multiloculated mass with individual
cavities small and filled with serous fluid; cut
surface is spongy.
Microscopically,
Multiple small cysts lined by small, flat or cuboidal cells
with abundant amount of glycogen.
A layer of myoepithelial cells present.
Prominent vascularization is present.
Ultrastructurally, prominent microvilli seen
Immunohistochemically, reactive for EMA, LMW
keratin, alpha-inhibin, NSE, MUC6, calponin
Fliud has a low level of CEA level.
Excision is curative
37. MUCINOUS CYSTIC NEOPLASMS
Seen in younger age group than microcystic
tumours
Predominant in women
Mostly in body and tail
Two categories: mucinous cystadenoma &
mucinous cystadenocarcinoma
Large multilocular cyst lined by tall columnar mucin
producing cells, often forming papillae
Stroma is very cellular resembling that of ovarian
stroma(also phenotypically)
38. Mucinous cystadenoma of
pancreas. The lesion is unilocular
and contains abundant inspissated
mucin.
Mucinous cystadenocarcinoma. This
tumor, which was invasive at the
microscopic level, shows areas of
hemorrhage and solid growth.
39. Mucinous cystadenoma of pancreas. The lining is monolayered
and made up of well-differentiated mucinous epithelium.
41. Diagnosis of malignancy regquires presence of
invasion of wall by neoplastic gland and frank
anaplasia of superficial component.
Aspiration of fluid: tall columnar cells, higher levels
of CEA & lower levels of elastase1.
Total excision is recommended.
Metastasis: usually restricted to abd. Cavity.
Histochemically, expression of MUC5AC, MUC2
with lack of MUC1
42. INTRADUCTAL PAPILLARY MUCINOUS
NEOPLASMS & PANIN
Distinct type of intraductal pancreatic tumour
Interplay of two factors : epithelial proliferation and
mucinous secretion
WHEN EPITHELIAL PROLIFERATION PREDOMINATE
Multicentric involvement of major ducts with papillary lesion,
cribriform pattern and cytologic atypia
Two subtypes: gastric & intestinal
WHEN MUCINOUS SECRETION PREDOMINATES
Gross dilatation of ducts filled with mucus
Microscopically, epithelium is columnar, mucous secreting
and well differentiated
43. Gross appearance of intraductal papillary carcinoma. The
tumor massively involves several major pancreatic ducts
45. Mucus-hypersecreting intraductal carcinoma. There is marked
dilation of a major pancreatic duct accompanied by fibrosis and
atrophy of the surrounding parenchyma. This duct contained large
amounts of mucin in its lumen.
46. Microscopic appearance of the same case showing a papillary
configuration associated with mucin hypersecretion.
47. Progression : spread slowly & eventually progress
to invasive adenocarcinoma
Histochemically, heterogenous mucin expression
At molecular level, mutations of K-RAS gene,
overexpression of HER2 product. Protein product of
DPC4 gene is present in all cases.
Main D/D : mucinous cystic neoplasms (female
predominance, no communication with ducts,
ovarian type stroma)
48. PANCREATIC INTRAEPITHELIAL NEOPLASIA
(PANIN)
This entity is very similar to IPMN
Relate to caliber of duct : large for IPMN & small for
PanIN
Thus, IPMN is , as a rule, clinically detectable,
grossly visible with grossly identifiable mucin and
well formed papillae AND reverse is true for PanIN.
49. ACINAR CELL TUMOURS AND TUMOUR LIKE
CONDITIONS
ACINAR CELL HYPERPLASIA
Incidental finding
May be confused with langerhans islets
50. ACINAR CELL ADENOMA
Solid pattern of growth
Entity of very doubtful existence
ACINAR CELL CYSTADENOMA
Uni/multicystic lesion lined by well differentiated acinar
cells
Usually not connected with pancreatic ductal system.
ACINAR CELL CARCINOMA
Uually in adults
Intraabdominal mass with or without jaundice
Widespread subcutaneous fat necrosis
51. Grossly, relatively well circumscribed fleshy mass,
avergaing 11 cm in diameter, with hemorrhage and
necrosis.
Microscopically,
Cellular without desmoplastic stroma
Pattern: solid, trabecular, glandular, papillary
Nuclei round to oval, only mild pleomorphism, single
prominent nucleoli & variable mitotic activity
Cytoplasm-abundant, eosinophilic granular
PAS positive diastase resistant zymogen granules
Immunoreactivity for trypsin, chymotrypsin, lipase,
amylase, anti- BCL10
52. Acinar cell carcinoma. The cut surface is solid and has a necrotic center. It
lacks the fibrous component usually seen in ductal adenocarcinoma.
53. Acinar cell carcinoma
of the pancreas
showing a well-
differentiated acinar
arrangement of the
tumor cells.
54. Acinar cell carcinoma showing a trabecular pattern of growth
that may be confused with that of an endocrine tumor.
56. SOLID-PSEUDOPAPILLARY TUMOUR
Also known as papillary and solid epithelial
neoplasm.
Common in young women
Grossly, large tumour with well developed capsule
with areas of hemorrhage and necrosis on cut
surface.
Microscopically, very cellular.
Pseudopapillae covered by several layers of epithelial
cells with thick fibrovascular core having prominent
mucinous changes
Nuclei are ovoid & folded with indistinct nucleoli and few
mitosis.
58. Solid and pseudopapillary tumor of pancreas. Note the
accumulation of myxoid material around the vessels.(high power
view)
59. Immunohistochemically, reactive for keratin,
vimentin, desmoplakin, trypsin, insulin &
glucagon(capacity for dual differentiation)
Progesterone receptors positive.
Genetically, β-catenin gene mutation.
Treatment is surgical
Overall prognosis is excellent.
60. PANCREATOBLASTOMA
Most common pancreatic neoplasm in childhood.
In some cases, asso. with beckwith-wiedmann syn
and familial adenomatous polyposis of colon
Bimodal age: mean- 2.4 & 33 years.
Grossly, avg tumour size is 10 cm & partial
encapsulation is the rule.
Microscopically, very cellular tumour
Solid sheets and nests of uniform epithelial cell with well
formed acinar structure and dilated ductular formations.
‘SQUAMOID CORPUSCLES CONSTANT AND
CHARACTERISTIC
Stroma abundant.
61. Pancreatoblastoma showing a predominantly solid pattern of growth
but also small rosette-like glandular formations.
63. Immnunohistochemically,
Evidence of acinar, endocrine and ductal differentiation.
AFP
Squamoid corpuscles : CK8/18/19, EMA positive
Genetically,
Nuclear translocation of β catenin
Loss of heterozogosity of chromosome 11p
Prognosis in infants is favourable.
65. GENERAL CLINICAL FEATEURES
Tradinitionally designated as islet cell tumours
Many arise from primitive multipotent cells located
within ducts.
Most occur in adults.
Many associated with MEN syndromes, VHL
disease, neurofibromatosis type 1 or tuberous
sclerosis
66. GENERAL MORPHOLOGIC FEATURES
Common location : body & tail of pancreas.
Grossly, pinkish cast resembling spleen or
congested lymphnode.
No well defined capsule.
May contain large amount of fibrous tissue,
calcification and bone.
Microscopically,
Small relatively uniform, cuboidal cells with centrally
located nuclei and acidophilic finly granular cytoplasm.
Nuclear enlargement and other abberations.
67. 4 patterns : solid, gyriform, glandular and
nondescript
reffered to as A/B/C/ &D or 1/2/3/4
Relation with further types :
predominantly gyriform – beta/alpha cell type.
glandular – G or VIP cells.
solid tumours – any cell type.
Stroma– highly vascular
Abundant hyaline material may be seen.
Amyloid in insulin secreting neoplasm(IAPP)
68. CLINICALLY,
May be nonfunctional or functional
Immunohistochemically,
Reactive for epithelial markers(CK7 CEA,)
Panendocrine markers
NESP-55
Markers specific for various peptide hormones.
Genetically
6q loss, mutation in MEN1 gene, allelic loss of 11q,
NO inactivation of DPC4
69. SPECIFIC TYPES
BETA CELL TUMOURS
Most common & better
< 10 % affected by MEN 1.
Presents with whipples traid when functional.
90% solitary, 70% measures 1.5 cm or less
Microscopically, gyriform or solid pattern.
Ultrastructurally, dense core secretory granules.
Immunohistochemically, reactive for insulin,
proinsulin,
As a rule malignant variety has shorter history &
more pronounced hypoglycemia.
71. ALPHA CELL TUMOURS
Two types
1) associated with glucagonoma syndrome
Solitary and large
Non discript microscopic pattern
Atypical granules ultrastructurally
Few cases positive for glucagon.
2)tumours not associated with glucagonoma syndrome
Often multiple & small
Gyriform pattern of growth
Strongly reactive for glucagon
Typical alpha granules
72. Gross appearance of alpha cell tumor (glucagonoma). The
tumor shown exhibits foci of hemorrhage and necrosis
73. Alpha cell tumor showing a prominent gyriform arrangement of the
tumor cells. Tumors with this pattern are usually composed of either
alpha or beta cells.
74. G – CELL TUMOUR
Can produce Zollinger-Ellison syndrome as a result
of excessive production of gastrin & reffered to as
gastrinoma.
Common site- pancreas followed by duodenal wall
and gastric antrum.
Solitary and often clinically malignant.
Microscopically, solid and or glandular.
IHC- gastrin production
76. OTHER TUMOURS OF ENDOCRINE PANCREAS
VIP producing tumours
DELTA CELL TUMOURS –somatostatin secretion
PP CELL TUMOURS -- secondary or minor
component in other tumours
CARCINOID TUMOURS– analogous to other
carcinoid tumours seen in G.I . Tract.
SMALL CELL CARCINOMA—similar to its more
common pulmonary counterpart.
77. BEHAVIOUR & PROGNOSIS
WHO has proposed three categories :
1. Well differentiated endocrine tumours
A. Benign behaviour
without extrapancreatic spread or vascular invasion
<2 cm in size,
<2 mitosis/10hpf,
<2% ki-67 positive cells
B. Uncertain behaviour
without extrapancreatic invasion
>2 cm in size,
angioinvasive and perineural invasion
2-10 mitosis /10hpf,
>2% ki-67 positive cells.
78. 2. Well differntiated low grade carcinoma
any tumour with gross local invasion &/or
metastasis.
further subdivided into functioning and non-
functioning .
3. Poorly differentiated endocrine carcinoma
also includes small cell neuroendocrine carcinoma
79. Tumours Age/sex Gross microscoic IHC
Ductal
adenocarcino
ma
Elderly/ M>F Solid, Poorly
delineated,
fibrosis in surr
ound. Area
Malignant
glands with
invasion
Mucins :
MUC1, CA-
19-9, CEA,
CKs
Anaplastic
carcinoma
>50yrs/M>F Large h’gic
tumour
3 patterns CK, CEA,
EMA
Microcystic
neoplasms
6th/7th
decade,
F>M
Large
multilocular
cystic tumour,
serous fluid
Small cysts
lined by
cuboidal epi.
With or
without atypia
CK, EMA,
MUC6, fliud
CEA level
Mucinous
cystic
neoplasm
5th/-6th
decade,
F>M
Large cysts,
mucin filled
Cysts lined by
columnar epi
+ ovarian
type stroma
MUC5AC,
MUC 2, fluid
CEA level
SUMMARY
80. Tumours Age / sex Gross Microscopic IHC
IPMN Elderly Involvemenat
of ducts,
papillary
lesion or
dilatation
Epithelial
proliferation or
mucus
secretion
Heterogenous
mucin
expression
Acinar cell
carcinoma
Adults Well
circumscribed,
fleshy, large
Solid, cellular
variable
patterns
trypsin,
chymotrypsin,
lipase,
amylase, anti-
BCL10
Solid
pseudopapillar
y tumour
Young
women, F>M
Large
encapsulated
with h’ge &
necrosis
Pseudopapilla
e thick
fibrovascular
core having
mucinous
changes
keratin,
vimentin,
desmoplakin,
trypsin, insulin
& glucagon
Pancreatoblas
toma
Bimodal
age(2.4 & 33
yrs)
Large(~10
cm), partially
encapsulated
Solid sheets
of epi. Cells +
squamoid
AFP,
CK8/18/19,
EMA
81. REFERENCES
ROSAI AND ACKERMAN’S SURGICAL
PATHOLOGY/tenth edition/chapter 15
ROBBINS & COTRAN/ PATHOLOGIC BASIS OF
DISEASE/south asia edition/9th edition/chapter 19
Internet
