1. PODOPLANIN IN TUMOR INVASIONPODOPLANIN IN TUMOR INVASION
– A PROMISING NEW APPROACH– A PROMISING NEW APPROACH
DR RATNADEEP GANGULY
MD, DNB, MIAC, MNAMS
Consultant Surgical Pathologist
DR TIBAR BANNERJEE
MS, MCh
Consultant Plastic Surgeon
THE MISSION HOSPITAL
Durgapur, INDIA

2. PATIENT #1
42y/male, papillomatous growth,
right side of cheek
Leukoplakia, left side

4. DIAGNOSIS
Papillomatous growth
Microinvasive squamous cell carcinoma, max
depth of invasion 2mm from BM
Leukoplakia
Squamous hyperplasia, keratosis without
dysplasia, no invasive ca

5. PATIENT #2
38y/male,
ulceroproliferative growth
in oral cavity

7. DIAGNOSIS
Ulceroproliferative growth – Squamous cell
carcinoma, appearing moderately differentiated in
this biopsy

8. DIAGNOSTIC PITFALLS WITH ONLY
HISTOMORPHOLOGICAL EXAMINATION
 Well oriented sections as opposed tangential sections
 Inflammation, edema & fibrosis around invasive nests
 Certain parameters subjective
 Detached nests of benign mucosa
 Dysplastic mucosa in head/neck may be a little
thickened appearing like a mass
 Squamous mucosa forming in salivary acini

9. PATTERNS OF TISSUE INVASION
SINGLE CELL INVASION
 Mimics early developmental process
(epithelial-mesenchymal transition)
 Loss of E-cadherin expression
COLLECTIVE CELL MIGRATION
 Less well understood
 Podoplanin expression
 Upregulated at the edges of large
tumor masses eg. SCC of lip, oral
cavity, ovarian granulosa cell tumor,
mesothelioma

10. SINGLE CELL INVASION LOSS OF
E-cadherin(BROWN) NO
PODOPLANIN
COLLECTIVE CELL MIGRN
NO
LOSS OF E-cadherin
PODOPLANIN(RED) AT
ADVANCING EDGE

11. WHAT IS PODOPLANIN ?
 Protein expressed in most human tissues
 Upregulated in tumor edges
 Bypasses epithelial-mesenchymal transformation in
carcinogenesis
 Promotes tumor cell spreading, migration &
invasion

12. WHAT IS PODOPLANIN ? – contd.
 SCC, CNS tumors & germinal neoplasms are +ve
 Collective cell migration - +ve
 Invasion of single cells / small cell groups
(Adenocarcinomas) - –ve
 Good adjunct in detection of equivocal invasion /
microinvasion in SCC of skin, lip, oral cavity

13. OTHER MEANS TO DETECT TUMOR INVASION
DEMONSTRATION OF BASEMENT MEMBRANE / BASAL
CELL LAYER BY:
Cytochemistry:
 Methenamine silver stain (black reticulin fibers)
 PAS reaction (magenta)
Immunohistochemistry:
 Collagen type IV & VII
 Laminin
 High mol wt cytokeratin (HMWCK - 34Eβ12) – Basal layer
Basement membrane
Basement
membrane

14. COLLAGEN TYPE IV IN BLOOD VESSEL -
IMMUNOHISTOCHEMISTRY