The document discusses pathology of oral cancer, including histological features and classifications. It notes that over 90% of oral cancers are squamous cell carcinoma, which can be well, moderately, or poorly differentiated. Other variants include verrucous, basaloid, and sarcomatoid squamous cell carcinoma. Prognostic factors discussed include tumor size and extent, lymph node involvement, histologic grade, and the presence of perineural or vascular invasion. Accurate classification of histologic type and grade is important for determining prognosis and treatment for oral cancers.

1. PATHOLOGY OF
ORAL CANCER

2. • Multiple anatomic sites in a limited area
• > 90 % are Squamous – Many Subtypes
• Among the remaining 10 % - Other varieties
INTRODUCTION

3. Epithelial tumours and lesions
Squamous cell carcinoma
Oral epithelial dysplasia
Low grade
High grade
Proliferative verrucous leukoplakia
Papillomas
Squamous cell carcinoma
Condyloma acuminatum
Verruca vulgaris
Multifocal epithelial hyperplasia
Tumours of uncertain histogenesis
Congenital granular cell epulis
Ectomesenchymal chondromyxoid tumour
Soft tissue and neural tumours
Granular cell tumour
Rhabdomyoma
Lymphangioma
Haemangioma
Schwannoma
Neurofibroma
Myofibroblastic sarcoma
Oral mucosal melanoma
Salivary type tumours
Mucoepidermoid carcinoma
Pleomorphic adenoma
Haematolymphoid tumours
CD30-positive T-cell lymphoproliferative disorser
Plasmablastic lymphoma
Langerhans cell histiocytosis
Extramedullary myeloid sarcoma
WHO classification of
oral tumor

4. Histologic alterations in
epithelial dysplasia
• Enlarged nuclei and cells
• Increased nuclear-to-cytoplasmic ratio
• Hyperchromatic nuclei
• Pleomorphic (abnormally shaped) nuclei and cells
• Increased mitotic activity
• Abnormal mitotic figures
• Multinucleation of cells
• Keratin or epithelial pearls
• Loss of typical epithelial cell cohesiveness
Sapp, Eversole, & Wysocki (2004). Contemporary oral and maxillofacial pathology (2nd ed.) St. Louis: Mosby Neville, Damm, & Bouquot (2002). Oral
and maxillofacial pathology (2nd ed.) Philadelphia: Saunders

5. Sapp, Eversole, & Wysocki (2004). Contemporary oral and maxillofacial pathology, 2nd ed. St. Louis: Mosby, p.
181
Histologic alterations observed in
epithelial dysplasia

6. Architectural
changes in epithelial
dysplasia
•Bulbousretepegs
•Basilarhyperplasia
•Hypercellularity
•Alteredmaturation
pattern of
keratinocytes
Neville, Damm, & Bouquot (2002). Oral and maxillofacial pathology (2nd ed.) Philadelphia: Saunders
Sapp, Eversole, & Wysocki (2004). Contemporary oral and maxillofacial pathology (2nd ed.) St. Louis: Mosby

7. COVENTIONAL SCC
90% of oral cancers
Histopathological Types
Well differentiated
• Contains well differentiated squamous cells,
arranged as islands with different shapes and
sizes, with keratinous pearls inside,
determined by a process of neoplastic
maturation.
• Cells are acidophil with pyknotic nuclei and
karyolysis, while the rest of the cells has nuclei
of different shapes and sizes, bigger than
normal epithelial nuclei.

8. COVENTIONAL SCC
Moderately differentiated
• organized in islands of neoplastic atypical
epithelial cells, oval-shaped, oblong, round
which infiltrated the tumoral stroma.
• At the periphery, carcinoma islands are
separated by fibrous stromal elements or
inflammatory type cells.
• Nuclei has different shapes and sizes, most
of them hypochromic with large nucleoli.

9. COVENTIONAL SCC
Poorly differentiated
• designed as cellular cords, islands or
epithelioid-like cells of various shapes
and sizes, with a different design from
the normal epithelium.
• The various aspects of cancer cells
means the malignant tumors are
heterogeneous entities, multicellular,
containing multiple cell lines who
interact with each other and with the
extracellular matrix

10. Varients of SCC
• Verrucous SCC
• Basaloid SCC
• Sarcomatiod SCC
• Adenosquamous SCC
• Adenoid SCC
• Papillary SCC
• Lympho-epithelial (nasopharyngeal- type ) carcinoma.

11. VERRUCOUS CARCINOMA
SITE :
• mucous membrane of head and neck (oral cavity and larynx )
• cutaneous surfaces in aero digestive tract, anogenital region and
lower extremities.
FEATURES
• May be both persistent and progressive that last for years.
• VSCC comprises about 3% of all SCC
• Appear suddenly or period of slow growth followed by rapid
enlargement.

12. MICROSCOPICALLY
 locally invasive with papillary folds.
 highly differentiated squamous epithelial cells.
 Surface of lesion is usually covered by
prominent keratin layer arranged in
compressed invagination folds
 Continuity is maintained by filiform or broader
processes of well differentiated squamous
cells.
 Infiltrative margins are blunt pushing
ones with good circumscription.
 Aassociated inflammatory reactions in stroma
consisting of lymphocytes.

13. Prognosis
• The prognosis is excellent
• Only by local recurrences.
• Pure verrucous carcinoma does not have metastatic potential.
• However, approximately 20 percent of verrucous carcinomas are hybrid,
having an additional component of conventional SCC that confers
metastatic potential to it
• Hence VSCC should be usually treated as well differentiated SCC.

14. BASALOID SQUAMOUS CELL CARCINOMA
• Its an aggressive variant of squamous cell carcinoma.
• High Grade
• SITE : upper aero digestive tract, esophagus, anus uterine and cervix.
• Base of tongue , pyriform sinus and supraglotic larynx with
metastasis to cervical lymph nodes.
• It manifests both deep and lateral invasion.
• Clinically : BSCC even when small , are usually hard and centrally
ulcerated with submucosal infiltration.

15. MICROSCOPICALLY
• Its usually well to moderately differentiated and invasive
with severe squamous dysplasia present.
• The growth pattern of basaloid cells is lobular, but can also
be in cods or trabeculae.
• Prominent mitotic activity.
Prognosis
• highly aggressive.
• Nodal metastasis is detected at initial presentation in almost two-thirds of the patients, and
one-half of them develop distant metastasis with the lung being the most common site.
• This mandates a metastatic survey at initial diagnosis.
• Median survival is 18 months.

16. SARCOMATIOD CARCINOMA
• It’s the most common ‘spindle-cell malignancies’ of upper airwayand
digestive tract.
• Worse prognosis than conventional SCC
• SITE : mucosa of head and neck, larynx and oral cavity, Sino nasaltract,
pharynx and esophagus.
• Usually pedunculated or polypeptide masses, less often sessile or ulcero infiltrative
lesions.
• Surface is extensively ulcerated and covered by fibrinonecroticexudate of varying
thickness.
• Typically occurs as post radiation recurrence or 2nd primary

17. MICROSCOPICALLY
• Its usually demarcated and does not exhibit intermingling with spindle cell
component.
• Sarcomatous element mimic fibroscarcoma , synovial sarcoma,
leiomyosarcoma.
• The spindle cells are arranged in fasciculate myxomatous orstreaming growth
pattern.
• Multinucleated giant cells are
common which may be accompanied by
metaplastic or malignant
osseocartilaginous foci.
•They May be richly or sparsely
mitotic.

18. ADENOSQUAMOUS CARCINOMA
• It’s a ‘malignant tumor with features of both
adenocarcinoma and squamous cell carcinoma.
• Highly infiltrative and aggressive
• SITE : GIT , upper and lower respiratory tract, skin , genitourinary
tract. Oral cavity (floor of the mouth, tonsillar-palatine) ,larynx, and
paranasal sinus.
• Its undeniably an aggressive neoplasm with high mortality rate
after regional or distant metastases.

19. Histologically :
• Characterized by association of adenocarcinoma and squamous cell
carcinoma growing in separate or mixed patterns.
• Three basic types of cell types : basaloid , squamous, and
undifferentiated.
•Prognosis
• Its undeniably an aggressive neoplasm
with high mortality rate after regional
or distant metastases.
• Aggressive surgery with neck dissection
yields an approximate 55% 2-year
survival.

20. ACANTHOLYTIC CARCINOMA
• High risk cutaneous variant
• Neoplasm of skin and especially of sun exposed area of head and neck.
• Rare entity .there are less than 30 cases of ASCCs documented in the
international literature so far
• Poor prognosis
• SITES : mucosal sites- vermilion border of lips , tongue, oral mucosa ,
nasopharynx , Sino nasal tract and larynx.
Mardi, Kavita, and Narbir Singh. “Acantholytic squamous cell carcinoma of the oral cavity: A rare entity.” Journal of oral and
maxillofacial pathology : JOMFP vol. 18,Suppl 1 (2014): S128-30. doi:10.4103/0973-029X.141359

21. Acantholytic squamous cell carcinoma resulting
in a pseudo-glandular appearance
Histologically
• It shows pseudo glandular features.
• Adenoid feature is initiated in basal layer
of squamous epithelium.
• Manifested by suprabasal clefting and
acantholysis.
• Desmoplastic reaction – accessory finding.
Mardi, Kavita, and Narbir Singh. “Acantholytic squamous cell carcinoma of the oral cavity: A rare entity.” Journal of oral and
maxillofacial pathology : JOMFP vol. 18,Suppl 1 (2014): S128-30. doi:10.4103/0973-029X.141359

22. HPV ASSOCIATED SCC
• HPV-HNSCC has a basaloid infiltrating morphology with a prominent lymphoid
response and minimal desmoplastic reaction.
• The basaloid tumour cells lack intercellular bridging cytoplasmic keratinization and
show a high nuclear cytoplasmic ratio.
• Lymphnode metastasis and central necrosis with cystic tumour degeneration is
frequently encountered and the cysts may sometimes clinically mimic branchial cleft
cysts.

23. HPV ASSOCIATED SCC
• Morphological distinction of HPV SCC from classical basaloid SCC is
difficult. The basaloid SCC has an aggressive clinical course and needs to
be distinguished.
• HPV-associated cancers tend to have increased survival and better
outcomes.
• HPV positive tumors had improved 3-year overall survival (OS) and
disease-free survival (DFS) compared to patients with HPV negative
tumors

24. • Most frequent site parotid, followed by intraoral minor salivary glands.
• located on the palate, in the retromolar area, the floor of the mouth, the
buccal mucosa, the lips and the tongue.
• Most patients are in their early fifties.
• Grossly, the tumor is poorly circumscribed and measures from 3 to 5 cm
• The tumor is composed of glandular and epidermoid cells, the latter
characteristically of intermediate basaloid type.
Mucoepidermoid Carcinoma

25. • The histologic grading scheme is prognostically significant.
• Low-grade tumors - Well formed glandular structure and prominent mucin
filled cystic spaces, minimal celluar atypia, high proportion of mucous cells
• Intermediate grade- Solid area of epidermoid cells or squamous cells with
intermidiate basloid cells. Less cyst formation as compared to low grade
• High grade – Solid nets and cords of basaloid and epidermoid cells .Prominent
nuclear pleomorphism and mitotic activity is noted. Cystic and glandular
content less
Mucoepidermoid Carcinoma

26. • Prognosis
• 90 percent of the low-grade as compared to 42 percent of the high-grade
mucoepidermoid carcinoma patients were found to be alive at 10 years
after diagnosis
• Radical surgery is the treatment of choice for all high grade MECs, or
low/intermediate-grade tumors that are large and involve the bone
• Radiation therapy is used with surgery although this carcinoma seems to
be radioresistant.
• Radiation therapy should be added in high-grade tumors and for
patients with unclear surgical margins or for patients with positive lymph
nodes
Mucoepidermoid Carcinoma
Triantafillidou K et al. Mucoepidermoid carcinoma of minor salivary glands: a clinical study of 16 cases and review of the
literature. Oral diseases. 2006 Jul;12(4):364-70.

27. • a well-defined tumor characterized by its pleomorphic or
mixed appearance.
• There is intermixing of the clearly recognizable epithelial
component with mucoid, myxoid and chondroid component
• Most common in Parotid followed by Minor Salivary glands
PLEOMORPHIC ADENOMA

28. Histopathologically
• Epithelial and myoepithelial cells with
interspersed areas of mesenchymal
differentiation.
• Epithelial cells typically form duct-like
structures associated with non-ductal
cells presenting varying shapes and
forms.
• Myxoid, cartilaginous, hyaline, or
osseous differentiation is appreciated
in the stromal component.
• The stroma is presented as a mixture
of gland-like epithelium and
mesenchyma-like tissue in varying
proportions
PLEOMORPHIC ADENOMA

29. • Benign lesion with good prognosis
• Surgical excision is first line of treatment
• Studies have shown that RT can effectively eradicate
microscopic residual disease in patients with pleomorphic
adenomas.
• The likelihood of controlling gross tumor is significantly lower
so that every effort to obtain a total macroscopic resection
should be made before RT.
PLEOMORPHIC ADENOMA

30. • Rare, accounting for approximately 1% of all melanomas, and
25% of mucosal melanomas of the head and neck.
• They constitute only 0.5% of all oral malignancies.
• OMMs are usually painless and grow quickly and therefore
are diagnosed late in the course of the disease when the
lesions are already large.
• OMMs metastasize to regional lymph nodes early in the
course of the disease and spread to distant sites by
haematogenous dissemination, usually to lungs, bone, liver,
brain and skin.
Oral Mucosal Melanoma

31. • MM originates from benign intramucosal melanocytes that
reside in the mucosa o f the upper aerodigestive tract
• Due to the rarity o f the disease, the role of nodal metastasis
is confined to either present (N+) or absent (NO).
• At this time, the role o f extranodal extension (ENE) is
unknown
Oral Mucosal Melanoma

32. Oral Mucosal Melanoma

33. PROGNOSTIC FACTORS

34. PROGNOSTIC FACTORS
Factors Related to Primary Tumor
• Size
• Thickness
• Invasive front
• Margins of resection
• Vascular and perineural invasion
• Morphology
Well/poorly differentiated
Exophytic/endophytic
• Mitotic index
• Presence of carcinoma in situ
Regional Lymph Nodes
• Positive/negative
• Number of positive nodes
• Size of largest positive node
• Presence/absence of extracapsular
extension

35. • Record all 3 dimensionsgrossly-length,widthandthickness
• Maximum tumourdimension determines the ‘T’Stage
Tumor Size
5 years disease-specific survival for T1 - 95.7%
T2- 80.5%,
T3- 69.1%
T4- 60%.
The five-year survival for tumours in Stages I and II may be over 80%, but survival for patients
with later stage tumours (III and IV) is less than 60%.
AJCC 8th edition 2017

36. RCPathStandards & Data setsreporting Cancers, Nov2013
Maximum Tumour Dimension

37. • WHO Classification of Head and Neck tumours
[4th Edition 2017]
• Commonest type - Squamous cell ca conventional ( > 90 %)
• Variants of SCC (Verrucous, Basaloid, Spindle cell)
• Ca of Minor salivary gland origin
• other
HISTOLOGIC TYPE

38. • Conventional SCC – Well, Moderate, Poor
•Variants of SCC - intrinsic biologic potential & don’t require grading
• Salivary gland ca – Biologic behaviour type dependent
 Mucoepidermoid carcinoma – Low, Intermediate, High
 Adenoid cystic carcinoma – Grade I, II, III
CAP protocol 2017
HISTOLOGIC GRADE

39. Depth ofInvasion - DOI
• Tumour Thickness – Distance measured from the mucosal
surface of the tumour to deepest point of invasion of tumour
• Depth of Invasion – Distance measured from basement
membrane of the adjacent normal mucosa to deepest point
of invasion of tumour
 Better assessed on microscopy
 Reported in mm
 Strongest pathological predictor for locoregional recurrence
Tumour thickness underestimates aggressive potential. Hence, DOI is a better
predictive parameter than tumour thickness
CAP protocol 2017
DEPTH OF INVASION

40. To measure DOI establish horizon at level of BM of closest intact squamous mucosa.
Draw a ”plumb line” from the horizon
AJCC 8th Edition 2017

41. # 4.72 mm

42. Lydiatt et al, CACancerJClin,
2017;67:122-137
“Tumour thickness” & “DOI” should not be used interchangeably
In exophytic tumours, the tumour thickness is greater than DOI

43. In ulcerated carcinomas, tumour thickness is deceptively thinner than DOI
AJCC 8th Edition 2017

44. Lydiatt et al, CACancerJClin, 2017;67:122-137

45. M.Faisal et al, PLOS ONE,August 2018
DOI Local recurrence LN metastasis
1 – 5 mm 15 % 23 %
6 – 10 mm 20 % 34 %
> 10 mm 40 % 53 %
In early stage tongue SCC, DOI is a predictor of local
Recurrence and cervical nodal metastasis

46. • Margins - Specimen’ssurgicalmargins
- Separatelysent marginsbysurgeon
• rrelevantmucosal,skin,soft tissueandbonycutmarginsaretaken
• Marginsectionstakenperpendiculartoresectionplane
MRGINS

47. • Positive margin : Presence of invasive ca or ca in situ/
high grade dysplasia at the margin
• Close margin : Cut –off 5 mm
• Close margin carries an increased risk for local
recurrence
• Margins from the main resection specimen have more
reliable prognostic value than separately taken tumour
bed margins.
CAP protocol 2017
MRGINS

48. Shah A.K JOMFP 2018;22:78-85

49. • Pattern of invasion is a validated outcome predictor for oral cavity
squamous carcinoma patients in multivariate analysis.
• Patterns of invasion
• Pattern of invasion (POI) assessed at tumor-host interface
• Bryne et al described 4 patterns (POI 1- 4)
• Brandwein-Gensler et al introduced POI 5 (POI 1-5)
Pattern of invasion

50. Pattern of invasion
Type
Type 1 pattern is cohesive in the form of ‘pushing’ bulbous rete pegs
which tend to infiltrate at the same level
Type 2 shows infiltrating cords, strands or large islands which tend to be
branching and continuous with the main tumour mass
Type 3 pattern shows small islands and cords which are separated from
the main tumour
Type 4 widely infiltrating small islands and single cells
Type 5 Worst pattern of invasion

51. • To simplify prognostication and enhance adaptation, the only cutpoint
recommended for assessment is whether or not WPOI-5 is present.
• WPOI-5 is defined as tumor dispersion of > 1 mm between tumor
satellites.
Worst Pattern of invasion
WPOI -5 : Tumour dispersion 1 mm or more between tumour satellites with iintervening normal tissue
# 2.69 mm

52. • With respect to low-stage oral cavity squamous carcinomas > 4 mm DOI,
the presence of WPOI-5 is significantly predictive of locoregional
recurrence and disease-specific survival
• Tumor dispersion is assessed at the advancing tumor edge.
• The most common WPOI-5 phenotype is tumor dispersion through soft
tissue.
• Dispersed extratumoral perineural invasion, or extratumoral
lymphovascular invasion, also can qualify for classification as WPOI-5.
Worst Pattern of invasion

53. In low stage oral SCC having WPOI 5, the probability of
developing locoregional recurrence is almost 42 %
Yufeng Li ,et al. Head & Neck Pathol (2013) 7:211-223

54. Alamangush A. Virchows Arch .2015 July;467(1):39-46
In early stage cancers, DOI > 4 mm & WPOI 5 are strongest
predictors for locoregional recurrence & mortality
In early stage (T1/T2) tongue cancers, despite early diagnosis
& treatment, 20 % patients still die of their disease

55. • Defined as presence of isolated tumour cells or small clusters (< 5
tumour cells) ahead of invasive tumour front
• Intensity of tumour budding :
- Low (< 5 buds/field using x20 objective lens)
- Intermediate (>= 5 to 10 buds/field)
- High (>= 10 buds/field)
• Budding represents two malignant features : cellular discohesion and
active invasion
TUMOR BUDDING

56. Tumour budding is an independent predictor of regional metastasis in early stage oral SCC
5 yr Disease Free Survival rate : 65.0 % for low intensity tumour budding
: 37.5 % for intermediate intensity tumour budding
: 23.1 % for high intensity tumour budding
Shota Shimizu ,et al. PLoS (2018) ;13(4):e0195451

57. • Important predictor of poor prognosis in head and neck cancer of virtually all
sites.
• The presence of perineural invasion in the primary cancer is associated with poor
local disease control and regional control, as well as being associated with
metastasis to regional lymph nodes.
• Further, perineural invasion is associated with decrease in disease-specific survival
and overall survival.
• The relationship between perineural invasion and prognosis is independent of
nerve diameter.
• Additionally, emerging evidence suggests that extratumoral perineural invasion
may be more prognostically relevant.
PERINEURAL INVASION

58. • Although perineural invasion of small unnamed nerves may not produce clinical
symptoms, the reporting of perineural invasion includes nerves of all sizes
including small peripheral nerves (ie, less than 1 mm in diameter).
• Aside from the impact on prognosis, the presence of perineural invasion also
guides therapy.
• Concurrent adjuvant chemoradiation therapy has been shown to improve
outcomes in patients with perineural invasion .
• Given the significance relative to prognosis and treatment, perineural invasion is a
required data element in the reporting of head and neck cancers.
PERINEURAL INVASION

59. • Moderately advanced local disease : 'T' stage - pT4a
• Bone invasion - Present or absent
- If present : Cortical / medullary
• Skin invasion - if present must be documented
Involvement of Bone / Skin

60. EROSIVE FORM:
• The bone recedes before a pushing tumor margin. E.g. :
Verrucous Carcinoma .
• There is loss of cortical continuity with a U-shaped or scalloped
excavation of medullary bone.
• Radiologically , there is well defined radiolucency with no spicules of bone
INFILTRATIVE FORM :
• There is neoplastic spread into the cancellous bone.
• Radiographically , ill-defined and irregular lesion is seen.
3. This shows spread through bone marrow without any marked destruction and
minimal radiographic changes. E.g.: adenoid carcinoma.
Involvement of Bone

61. • Total number of nodes at each level
• Number of nodes showing metastasis at each level
• Size of largest metastatic deposit
• Extranodal extension (ENE) – Present / Absent
Lymph nodes involvement

62. Lymph nodes involvement

63. ExtraNodal Extension
• The status of cervical lymph nodes is the single most important
prognostic factor in aerodigestive cancer.
• All macroscopically negative or equivocal lymph nodes should be
submitted in toto.
• ENE is defined as extension of metastatic carcinoma within lymph
node, through the capsule, and into the surrounding connective
tissue, regardless o f associated stromal reaction.
• Histopathologic designations for ENE are as follows:
• ENEn (none)
• ENEmi (microscopic ENE < 2 mm)
• ENEma (ENE>2 mm or gross ENE)
ExtraNodal Extension

64. • ENE is extension of metastatic ca from within a LN through fibrous
capsule into surrounding connective tissue, regardless of presence or
absence of stromal reaction
• ENE is measured as maximum distance in mm from outer aspect of
intact or reconstructed nodal capsule to the farthest point of
extranodal invasion
CAP protocol 2017
• Metastatic carcinoma that stretches capsule but does not breach it,
doesn’t account for ENE
• Soft tissue tumour deposit in lymphatic drainage area is recorded as a
positive LN with ENE
ExtraNodal Extension

65. Clinical relevance of prognostic parameters
• Postoperative radiation – Intermediate/high risk factors
- Advanced tumour stage – T3/T4
- Positive/close resection margin
- ENE
- DOI > 5 mm [ For tongue & FOM DOI > 4 mm]
- N2/N3 LNs
- PNI & LVI
- Level IV/V LN involvement
• Postoperative chemoradiation – High risk factors
- Positive resection margin
-PNI
- ENE
-
NCCN 2018 ,Shruti Jolly et al UpToDate April 2018

66. • AJCC Protocol 2017 8th Edition
• WHO classification 2017
• RCPath Standards & Data sets reporting Cancers, Nov 2013
• NCCN 2018 ,Shruti Jolly et al UpToDate April 2018
• CAP protocol 2017
• Shota Shimizu ,et al. PLoS (2018) ;13(4):e0195451
• Alamangush A. Virchows Arch .2015 July;467(1):39-46
• Sapp, Eversole, & Wysocki (2004). Contemporary oral and maxillofacial pathology (2nd
ed.) St. Louis: Mosby Neville, Damm, & Bouquot (2002). Oral and maxillofacial
pathology (2nd ed.) Philadelphia: Saunders
• Mardi, Kavita, and Narbir Singh. “Acantholytic squamous cell carcinoma of the oral
cavity: A rare entity.” Journal of oral and maxillofacial pathology : JOMFP vol. 18,Suppl
1 (2014): S128-30. doi:10.4103/0973-029X.141359
• Triantafillidou K et al. Mucoepidermoid carcinoma of minor salivary glands: a clinical
study of 16 cases and review of the literature. Oral diseases. 2006 Jul;12(4):364-70.
• Yufeng Li ,et al. Head & Neck Pathol (2013) 7:211-223
• M.Faisal et al, PLOS ONE, August 2018
REFERANCES

67. THANK YOU