LinkedIn emplea cookies para mejorar la funcionalidad y el rendimiento de nuestro sitio web, así como para ofrecer publicidad relevante. Si continúas navegando por ese sitio web, aceptas el uso de cookies. Consulta nuestras Condiciones de uso y nuestra Política de privacidad para más información.
LinkedIn emplea cookies para mejorar la funcionalidad y el rendimiento de nuestro sitio web, así como para ofrecer publicidad relevante. Si continúas navegando por ese sitio web, aceptas el uso de cookies. Consulta nuestra Política de privacidad y nuestras Condiciones de uso para más información.
4) variations in pancreaticobiliary anatomy
5)Age : elderly
6)Sex : male:female—1.6:1
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
LOCATION & GROSS FEATURES
2/3 rd – head of the pancreas
1/3 rd – body & tail of pancreas
Multiple tumours in 20 % of cases
- poorly delineated, firm
- yellowish grey cut surface
- rarely massive cystic degeneration
- pancreatic ducts- dilated and plugged with
- extrapancreatic extension is common
Gross appearance of typical invasive ductal carcinoma of the head of
the pancreas. The tumor is protruding into the duodenal lumen.
Grading- well/moderately/ poorly defferentiated
Low power view-
well formed glands, with large lumen, lined
by one or few layers of cylindrical or cuboidal
irregularities in shape & distribution of
glands, prominent concentric desmoplastic
stroma surrounding the glands.
Pancreatic ductal adenocarcinoma.:It is typical of this tumor type to
be well differentiated architecturally(low power view)
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,
Carcinoma in situ( high grade pancreatic intra
epithelial neoplasm) & atypical hyperplasia
Lobular tissue destroyed, islet cell preserved –
Pancreatic ductal adenocarcinoma.:It is typical of this tumor type to be
well differentiated architecturally but to show marked cytologic atypia
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
Overexpression of HER2
Loss or overexpression of DNA mismatch repair
Mucin-producing adenocarcinoma of the pancreas
associated with large pools of extracellular mucin.
SPREAD AND METASTASIS
Peri pancreatic soft tissue
Invasion into the duodenum & common bile duct
Vascular & neural invasion
Overall 5 year survival rate is 4 % or less
Mean survival of 3 months
Factors related to prognosis are :
Tumour less than 4.5 cm in diameter– longest survival
Blood vessel invasion & retroperitoneal margin of
TGF- β1 expression– related to better differentiated
Cytokeratin 20 expression—decreased survival
Mapsin expression—better prognosis
SMAD4 gene mutation—worse prognosis
Also known as PLEOMORPHIC, SARCOMATOID
OR UNDIFFERENTIATED CARCINOMA
Highly distinctive morphology and highly aggressive
> 50 years, male predilection
Three morphologic types:
Large no. of bizzare multinucleated cells
Poor cellular cohesion(loss of E-cadherin expression)
Lymphnode & hematogenous metastasis common
2) tumour largly composed of spindle shaped cells
3)solid tumour of small monotonous round cells
Immunohistochemically, keratin, EMA & CEA
Prognosis : extremely poor
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.
GIANT CELL TUMOUR OF PANCREAS
Distinct morphologic appearance and better
Grossly, large and hemorrhagic
Microscopically, dual polulation :
Uniform spindle cells of mesenchymal origin with
Multinucleated giant cells (=osteoclasts)
Nuclei of osteoclast like cells are uniform small and
mitoses and bizarre forms are absent.
Gross appearance of giant cell tumor of pancreas. There is a large
hemorrhagic mass in the head of the pancreas that is protruding into
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
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
Also known as glycogen rich or serous
Usually in elderly
Some cases aassociated with VHL gene mutations
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.
Grossly, large multiloculated mass with individual
cavities small and filled with serous fluid; cut
surface is spongy.
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
High-power view of microcystic cystadenoma showing lining of
cuboidal epithelium with optically clear cytoplasm.
Microcystic appearance similar to that of adenoma.
Nuclear atypia, perineural invasion and aneuploid
DNA pattern present.
MUCINOUS CYSTIC NEOPLASMS
Seen in younger age group than microcystic
Predominant in women
Mostly in body and tail
Two categories: mucinous cystadenoma &
Large multilocular cyst lined by tall columnar mucin
producing cells, often forming papillae
Stroma is very cellular resembling that of ovarian
Mucinous cystadenoma of
pancreas. The lesion is unilocular
and contains abundant inspissated
Mucinous cystadenocarcinoma. This
tumor, which was invasive at the
microscopic level, shows areas of
hemorrhage and solid growth.
Mucinous cystadenoma of pancreas. The lining is monolayered
and made up of well-differentiated mucinous epithelium.
Mucinous cystadenoma with underlying ovarian-type stroma:
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
INTRADUCTAL PAPILLARY MUCINOUS
NEOPLASMS & PANIN
Distinct type of intraductal pancreatic tumour
Interplay of two factors : epithelial proliferation and
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
Gross appearance of intraductal papillary carcinoma. The
tumor massively involves several major pancreatic ducts
Microscopic appearance of the same case, showing a
complex papillary architecture
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.
Microscopic appearance of the same case showing a papillary
configuration associated with mucin hypersecretion.
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)
PANCREATIC INTRAEPITHELIAL NEOPLASIA
This entity is very similar to IPMN
Relate to caliber of duct : large for IPMN & small for
Thus, IPMN is , as a rule, clinically detectable,
grossly visible with grossly identifiable mucin and
well formed papillae AND reverse is true for PanIN.
ACINAR CELL TUMOURS AND TUMOUR LIKE
ACINAR CELL HYPERPLASIA
May be confused with langerhans islets
ACINAR CELL ADENOMA
Solid pattern of growth
Entity of very doubtful existence
ACINAR CELL CYSTADENOMA
Uni/multicystic lesion lined by well differentiated acinar
Usually not connected with pancreatic ductal system.
ACINAR CELL CARCINOMA
Uually in adults
Intraabdominal mass with or without jaundice
Widespread subcutaneous fat necrosis
Grossly, relatively well circumscribed fleshy mass,
avergaing 11 cm in diameter, with hemorrhage and
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
Acinar cell carcinoma. The cut surface is solid and has a necrotic center. It
lacks the fibrous component usually seen in ductal adenocarcinoma.
Acinar cell carcinoma
of the pancreas
showing a well-
arrangement of the
Acinar cell carcinoma showing a trabecular pattern of growth
that may be confused with that of an endocrine tumor.
Strong immunoreactivity for lipase in acinar cell carcinoma.
Also known as papillary and solid epithelial
Common in young women
Grossly, large tumour with well developed capsule
with areas of hemorrhage and necrosis on cut
Microscopically, very cellular.
Pseudopapillae covered by several layers of epithelial
cells with thick fibrovascular core having prominent
Nuclei are ovoid & folded with indistinct nucleoli and few
Solid and pseudopapillary tumor of pancreas. (low power
Solid and pseudopapillary tumor of pancreas. Note the
accumulation of myxoid material around the vessels.(high power
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.
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
Pancreatoblastoma showing a predominantly solid pattern of growth
but also small rosette-like glandular formations.
Pancreatoblastoma showing a large squamoid corpuscle
surrounded by small glands.
Evidence of acinar, endocrine and ductal differentiation.
Squamoid corpuscles : CK8/18/19, EMA positive
Nuclear translocation of β catenin
Loss of heterozogosity of chromosome 11p
Prognosis in infants is favourable.
GENERAL CLINICAL FEATEURES
Tradinitionally designated as islet cell tumours
Many arise from primitive multipotent cells located
Most occur in adults.
Many associated with MEN syndromes, VHL
disease, neurofibromatosis type 1 or tuberous
GENERAL MORPHOLOGIC FEATURES
Common location : body & tail of pancreas.
Grossly, pinkish cast resembling spleen or
No well defined capsule.
May contain large amount of fibrous tissue,
calcification and bone.
Small relatively uniform, cuboidal cells with centrally
located nuclei and acidophilic finly granular cytoplasm.
Nuclear enlargement and other abberations.
4 patterns : solid, gyriform, glandular and
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)
May be nonfunctional or functional
Reactive for epithelial markers(CK7 CEA,)
Markers specific for various peptide hormones.
6q loss, mutation in MEN1 gene, allelic loss of 11q,
NO inactivation of DPC4
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,
As a rule malignant variety has shorter history &
more pronounced hypoglycemia.
ALPHA CELL TUMOURS
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
Gross appearance of alpha cell tumor (glucagonoma). The
tumor shown exhibits foci of hemorrhage and necrosis
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.
G – CELL TUMOUR
Can produce Zollinger-Ellison syndrome as a result
of excessive production of gastrin & reffered to as
Common site- pancreas followed by duodenal wall
and gastric antrum.
Solitary and often clinically malignant.
Microscopically, solid and or glandular.
IHC- gastrin production
Rosette-like gland formation in G-cell tumor (gastrinoma).
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.
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% 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.
2. Well differntiated low grade carcinoma
any tumour with gross local invasion &/or
further subdivided into functioning and non-
3. Poorly differentiated endocrine carcinoma
also includes small cell neuroendocrine carcinoma
Tumours Age/sex Gross microscoic IHC
Elderly/ M>F Solid, Poorly
fibrosis in surr
>50yrs/M>F Large h’gic
3 patterns CK, CEA,
Cysts lined by
MUC 2, fluid
Tumours Age / sex Gross Microscopic IHC
IPMN Elderly Involvemenat
with h’ge &
age(2.4 & 33
of epi. Cells +
ROSAI AND ACKERMAN’S SURGICAL
PATHOLOGY/tenth edition/chapter 15
ROBBINS & COTRAN/ PATHOLOGIC BASIS OF
DISEASE/south asia edition/9th edition/chapter 19