pathological aspects of pre-invasive and invasive cervical cancer

1. pATHOLOGICALASPECT
OF PRE-iNVASIVE AND
iNVASIVE cERVICAL
LESIONs
- Dr. Prachi, M.D. (Pathology)
Junior Consultant
Department of Surgical Pathology and Laboratory Medicine
DNSH, New Delhi

2. INTRODUCTION
• Cervical cancer is one of the leading cause of cancer related death in women
aged <45years (one of the top three cancer).
• WHO global cervical cancer elimination initiative has the ambitious goals of
scaling up HPV vaccinations of the girls, screening for and treating pre-
cancerous lesions and providing access to and treatment of invasive cancers,
which carries substanstial impact on reducing the burden of cervical cancer.

4. WHO CLASSIFICATION OF UTERINE CERVIX
(2020)
Squamous epithelial tumors-
• Mimics of squamous precursor lesions
• Squamous metaplasia
• Atrophy of the uterine cervix
• Squamous cell tumors and precursors
• Condyloma acuminatum
• Squamous intraepithelial lesions of the uterine cervix
• Squamous cell carcinoma, HPV associated, of the uterine cervix
• Squamous cell carcinoma, HPV independent, of the uterine cervix
• Squamous cell carcinoma, NOS of the uterine cervix

5. Glandular tumors and precursors
-Benign glandular lesions
• Endocervical polyp
• Müllerian papilloma of the uterine cervix
• Nabothian cyst
• Tunnel clusters
• Microglandular hyperplasia
• Lobular endocervical glandular hyperplasia
• Diffuse laminar endocervical hyperplasia
• Mesonephric remnants and hyperplasia
• Arias Stella reaction of the uterine cervix
• Endocervicosis of the uterine cervix
• Tuboendometrioid metaplasia
• Ectopic prostate tissue

6. • Adenocarcinomas
• Adenocarcinoma in situ, HPV associated, of the uterine cervix
• Adenocarcinoma, HPV associated, of the uterine cervix
• Adenocarcinoma in situ, HPV independent, of the uterine cervix
• Adenocarcinoma, HPV independent, gastric type, of the uterine cervix
• Adenocarcinoma, HPV independent, clear cell type, of the uterine cervix
• Adenocarcinoma, HPV independent, mesonephric type, of the uterine cervix
• Other adenocarcinomas of the uterine cervix

7. • Other epithelial tumors
• Carcinosarcoma of the uterine cervix
• Adenosquamous and mucoepidermoid carcinomas of the uterine cervix
• Adenoid basal carcinoma of the uterine cervix
• Carcinoma of the uterine cervix, unclassifiable
• Mixed epithelial and mesenchymal tumors
• Adenomyoma of the uterine cervix
• Adenosarcoma of the uterine cervix
• Germ cell tumors
• Germ cell tumors of the uterine cervix

8. PATHOGENESIS OF HPV INFECTION
• 100 genetically distinct type of HPV.
• Low Risk- 1,2,4 and 7- Benign Squamous papilloma.
• High Risk – 16 and 18- Squamous cell carcinoma.
• Sexually transmitted Infection.

10. PATHOGENESIS SUMMARY
HPV –E6
HPV-E7
TERT
p53
p-21
RB
Increased Telomerase Expression
Inhibition of p-53
Inhibition of p-21 and p-27
Increased CDK4/cyclin
Inhibition of RB
-Immortalization
-Increased cell
Proliferation
- Genomic
Instability
Upregulation of p-16

11. KEY POINTS TO PATHOGENESIS
High-risk HPV types express
oncogenic proteins that inactivate
tumor suppressors, activate cyclins,
inhibit apoptosis, and combat cellular
senescence.

12. Immature Squamous Metaplasia- lacks maturation/
Glycogen deposition and presence of goblet like cells.
Mature Squamous Metaplasia- Glycogenated
epithelium
With underlying endocervical gland.
MIMICS OF SQUAMOUS PRECURSOR LESIONS

13. Squamous Metaplasia- Centrally placed nuclei with
distinct cell borders

14. Cervical Atrophy- Parabasal cells only without
maturation

15. CONDYLOMAACUMINATUM
-Benign verrucous papillary lesion caused by HPV.
-Papillomatosis, acanthosis, and hyperkeratosis and
Koilocytic Atypia.
-Localized on the vulvar skin, vestibule, perineum, and
Perianal skin.
-HPV6 and HPV 11 are the most prevalent types
Associated with the lesion
-Giant Condyloma Acuminatum, a.k.a-
BUSCHKE LOWENSTEIN TUMOUR..

16. Squamous intraepithelial lesions of the uterine
cervix.
• Proliferation of squamous cells driven by HPV infection showing maturation abnormalities and viral
cytopathic effects, limited by basement membrane.
• LSIL (CIN-1- Condyloma)- Mild Squamous Dysplasia
• HSIL (CIN-2,CIN-3)- strong predilection for squamo-columnar junction- Moderate to severe
squamous dysplasia.
Note-CIN terminology is obsolete now

17. LSIL (Low-grade SIL)
-Asymptomatic-5-10%prevalence
-Can be caused by HR/LR-HPV-Flat Lesions
-DNA-stable-Euploid or polyploid
-Koilocytic Atypia
-Acetowhite change, Iodine(-),punctuation,
mosaicism on colposcopy
Pathogenesis-
-Viral gene expression is coordinated with squamous differentiation
-HR-HPV –Overexpression of p-16-by E7 and RB-1 gene interaction.
-LR-HPV- Do not induce overexpression of p-16- absence of block positivity of p
-Immunosuppression and Smoking are risk factors.

18. DIFFERENTIAL DIAGNOSIS OF LSIL
• Benign squamous epithelium with reactive and inflammatory features resembles
LSIL, hence can be overdiagnosed in as many as 50% of cases, following which
demonstration of HPV-RNA –ISH is done. P-16 is of no significance at this interface, many
LSIL are negative.
• To distinguish between CIN-1 and CIN-2 (HSIL) is challenging, specially in tangential
section and in cases of partial denuded epithelium. P-16 should be used.
• Block type p-16 positivity in cases of HSIL, whereas absent in cases of LSIL.

19. A LARGE POPULATION-BASED STUDY REPORTED A 6.1% 5-YEAR RISK OF CIN 3+
FOR WOMEN WITH HPV-ASSOCIATED LSIL ON CYTOLOGY AND A 2.0% RISK WITH
HPV-INDEPENDENT LSIL. FOR WOMEN WITH A PAP TEST DIAGNOSIS OF HSIL, THE
5-YEAR RISK OF CANCER WAS 6.6–6.8%.

20. HSIL (High Grade SIL)
-0.5-1% -Prevalence
-DNA-labile-Aneuploidy
-More acetowhite and for longer duration as
compared to LSIL.
-PATHOGENESIS- Uncoordinated expression of
Viral E6 and E7 oncoproteins leading to genetic
and cellular abnormalities-upregulation of p-16.
P-16- Strong block type staining in basal
keratinocytes and extending beyond the lower
third of the epithelium.
-Patterns of HSIL-Thin, keratinizing, pleomorphic
and Papillary.
-Masquerading Lesions- Atrophy, Immature
Metaplasia (Benign) and Carcinoma.
A-Full thickness basal type atypia without evidence of
Maturation.
B-HSIL extending into endocervical glands, should not be
Interpreted as invasion.

22. APPLICATION OF P-16 IN SQUAMOUS
LESIONS
• It is recommended by Lower Anogenital Squamous terminology (LAST) standardization project in 3 specific
context-
1-Distinguishing HSIL from precancer mimickers (immature metaplasia, atrophy, tangential sectioning and
reparative changes).
2-To supplement morphological assessment of cervical biopsies specimen interpreted as < LSIL, that are at
high risk of missed high grade disease based on the prior PAP or HPV testing results.
3-To inform the diagnosis of LSIL versus HSIL (CIN-2) in morphologically equivocal staining- block type staining
supports HSIL.
NOTE-
1.OVERAPPLICATION OF P-16 SHOULD NOT BE DONE TO AVOID OVERDIAGNOSIS IN cervical biopsies
cases.

23. Prognostic Factors
• CIN II shows high spontaneous regression rate (42% and 50% at 12 and 24 months, respectively),
particularly in young women (< 30 years).
• CIN II progression risk to CIN III or worse increases with time (from 5% at 3 months to 24% at 36
months).
• CIN III confers highest risk for progression to invasive squamous cell carcinoma (up to 31% if
untreated) and lowest rate of spontaneous regression.
• Risk of HSIL after 2 consecutive high risk HPV+ tests = 17%
• Increases to 41% with 2 previous HPV 16+ tests

24. TREATMENT
• Cryotherapy
• Laser Ablation
• LEEP (Loop Electrosurgical excision procedure)-Resected margins should be assessed.
• Conisation
Testing for HPV-DNA at 6-12 months after therapy or even intra-operatively is the best predictor for
recurrent or residual disease.

25. SQUAMOUS CELL CARCINOMA OF THE
UTERINE CERVIX- HPV ASSOCIATED.
• 80-90% of cervical cancer are SCC.
• Median age-51 years.
• >90-95% cervical SCC are high risk-HPV related (12 HPV subtypes)
• HPV-16 and 18 responsible for 70-75% of SCC
• Risk Factors-Immunosuppression, multiparity, smoking and the use of oral
contraceptives
• Almost all HPV associated SCC shows strong and diffuse p-16 overexpression in

26. PATHOGENESIS OF SCC
• Genetic and Epigenetic alterations.
• Hypermethylation of CpG-islands in promoter regions of the tumour suppressor
gene.
• Genomic alteration in the PI3K/MAPK and TGF-Beta signalling pathways.
• Mutation in the ERBB3, CASP-8, HLA-A, SHKBP-1 and TGFBR2.

27. Grossly- Exophytic or Endophytic
A-Infiltrating nests of Tumour cells with/without keratinization with desmoplastic stroma
B-Strong and Diffuse Overexpression of p-16.
Histological Patterns-keratinizing, NonKeratinizing, Basaloid, Papillary, Squamo-transitional,Lympho

28. Large syncytial aggregates of tumour cells
With Karrhyorectic debris along the edges.
Papillary SCC- Fibrovascular core lined by multilayered atypical
Squamous epithelial cells
NOTE- Histological type doesn’t have any prognostic implication

29. SCC HPV-INDEPENDENT, OF THE UTERINE
CERVIX
• 5-7% of all SCC cervical cancer.
• PATHOGENESIS- p-53 mutation, KRAS, ARID1A, PTEN.
• Usually keratinizing morphologically (however any morphology can be seen)
• LOSS of p-16 immunostaining.
• Usually diagnosed at an advanced stage and prone for lymph node
metastasis, hence reduces the disease free and overall survival

30. SCC OF THE UTERINE CERVIX, NOS
• REPORTED WHEN P-16/HPV testing is not AVAILABLE
in PATHOLOGY Report.

31. ENDOCERVICAL POLYP
• BENIGN endocervical epithelium covering a fibrovascular core

32. MULLERIAN PAPILLOMA OF THE UTERINE
CERVIX
-Mullerian Papilloma of Infancy.
-Common in children, aged 2-5 years.
-Cervical or upper vaginal exophytic growth
-Branching fibrous papillae, lined by a single
layer of benign glandular epithelium, with or
without squamous metaplasia.

33. NABOTHIAN CYST
- Benign
- 2-10mm in size
- Asymptomatic, and may presents as polyp.
- Obstruction of the endocervical gland leads to mucus
retention and cyst formation.
- Mucus-filled cystic structure in the cervical
wall, lined by endocervical epithelium.
- Large or deeply situated nabothian cysts
can be clinically concerning for a
malignant process.

34. TUNNEL CLUSTERS
-Usually seen in 10% of adult women.
-Multiparous women
-Involutional change in the endocervical gland hyperpla
-Well demarcated lobular lesion, composed of
cystically dilated glands lined by flattened or
cuboidal mucus producing cells.

35. MICROGLANDULAR HYPERPLASIA
-Non- neoplastic hyperplastic endocervical lesion.
-Often associated with pregnancy and progesterone therap
-Closely packed variable sized glands lined by mucinous
epithelium with subnuclear vacuolation and reserve cell
hyperplasia and separated by scant, focally inflamed strom

36. LOBULAR ENDOCERVICAL GLANDULAR
HYPERPLASIA (LEGH)
• Occurs in patient with peutz jeghers syndrome (germline STK11 mutation)
• Mutation in KRAS, GNAS, STK11(Sporadic mutation).
• ATYPICAL LEGH may be associated with adenocarcinoma showing gastric
(pyloric gland) differentiation and is best treated as in situ neoplasia.

37. LOBULAR ENDOCERVICAL GLANDULAR
HYPERPLASIA (LEGH)
A-central cleft surrounded by a lobular proliferation of small to medium sized glands
B-Mucinous epithelium lined glands, C-Atypical LEGH

38. DIFFUSE LAMINAR ENDOCERVICAL
HYPERPLASIA
Well demarcated laminar proliferation of
angulated endocervical glands with surrounding
inflammation

39. MESONEPHRIC REMNANTS AND
HYPERPLASIA
Arises from residual cells of mesonephric Duct.
A-rounded aggregates of mesonephric tubules, B-Mesonephric hyperplasia, Ductal Type, C-Mesonephric remnant- tubules
With PAS positive eosinophilic secretion

40. ARIAS-STELLA REACTION OF THE UTERINE
CERVIX (ASR)
- PREGNANCY related hormones, GTD and high dose of
progestins
- Differential diagnosis- clear cell carcinoma and
adenocarcinoma in situ of cervix.
- No apoptotic bodies and mitosis- ASR.
- Enlarged glandular hobnail cells with vacuolated clear
cytoplasm, hyperchromatic nuclei and maintained N:C
ratio.
- Nuclear enlargement occurs due to increase in the
DNA ploidy due to hormonal stimuli.

41. ENDOCERVICOSIS OF UTERINE CERVIX
Due to previous history of caesarian section/surgery – causing
displacement of endocervical epithelium. Commonly present in
the bladder.
A- Dilated glands identified in the outer portion of the cervix
Adjacent to parametrium.
B-Deeply located glands lined by mucus producing columnar cells.

42. TUBOENDOMETROID METAPLASIA
Change from endocervical epithelium to tubal (ciliated) or endometroid type epithelium, associated with previous cervical
Instrumentation (Loop or Cone excision).
A-Tuboendometroid glands in the background of normal endocervix.
B-Lack of Overt mucinous differentiation and the presence of ciliated and non- ciliated pseudostratified epithelial cells

43. ECTOPIC PROSTATE TISSUE
-Derived from misplaced Skene glands or
androgen related Metaplastic process.
-Identical prostate glands in cervical
stroma.
-Immunohistochemically, the luminal cells
are variably positive for PSA, PAP,
AMACR, and NKX3-1, and the basal cell
layer is p63-positive; the glandular and
squamous elements are AR-positive

44. ADENOCARCINOMA IN SITU, HPV
ASSOCIATED OF THE UTERINE CERVIX
-99% are HPV-associated (16, 18 and 45)
-A/k/a High-grade cervical glandular
intraepithelial neoplasia.
-A- AIS-bland appearance of endocervical
Papillae, with focal overt nuclear atypia.
B-p-16- strong and diffuse.
C-Isolated nuclear atypia but an absence of
Mitotic activity or apoptosis.
D- p-16-block positivity in AIS, patchy in
Tubo endometroid metaplasia and no staining
in normal endocervical epithelium.

45. A- Stratified Mucin producing intraepithelial lesion
resembles HSIL.
B-AIS with depleted mucin, resemble endometroid
Adenocarcinoma, (but lacks the other confirmator
Features like squamous metaplasia, atypical
Hyperplasia)
C-AIS with Intestinal differentiation, decreases p-1
differentiation
D-AIS with pseudostratification resembling
Endometroid

46. -Morphology is sufficient for diagnosis, usually p-16 is not employed in AIS.
-p16 immunohistochemistry should be applied when there is diagnostic uncertainty involving
hyperplastic, reactive, and metaplastic lesions.
Other cases with block type p-16 positivity-
- Serous carcinomas of the endometrium or adnexa (95-100%)
- High Grade Endometroid carcinoma of Endometrium (about 1/3rd)
- Clear cell carcinoma of the endometrium and cervix (about 1/3rd)
Direct HPV testing is recommended as an adjunct to the morphology in majority
of cases showing equivocal p16 staining pattern or cases with block-type
staining of a lesion lacking the characteristic morphology of AIS.

47. A- Clusters of crowded glandular cells with overlapping of hyperchromatic nuclei and feathering.
B- Atypical Glandular epithelial cells.
C- AIS- feathering, Palisading and elongated and irregular nuclei.
Pap tests have a high false negative rate for the detection of endocervical
adenocarcinoma. Hence concurrent positive HPV testing is recommended.

48. DIAGNOSTIC AND MOLECULAR PATHOLOGY
-HR-HPV in situ hybridization will identify nuclear signals (DNA-based) or
nuclear and cytoplasmic signals (mRNA-based); mRNA-based in situ
hybridization is more specific than DNA-based methods.
-PCR may be used to confirm HPV infection, but sensitivity and specificity are
lacking because the analysis may underperform in archival formalin-fixed tissue
and does not provide for ascertainment that HPV is present, specifically, within
neoplastic cells.

49. ADENOCARCINOMA- HPV ASSOCIATED OF
THE UTERINE CERVIX
• 5% of all cervical carcinomas- in non- screened population.
• 10-25% in developed countries.
• Caused by HR-HPV- 16, 18 and 45.
• Pattern based classification (Silva System) of HPV associated Endocervical
adenocarcinoma- Pattern A, Pattern B and Pattern C.

50. PATTERN A-
-Well demarcated glands with rounded contours
-No lymphovascular Invasion.
-Complex intraglandular growth acceptable(i.e.,
cribriform growth and papillae
- Lack of Solid Growth

51. PATTERN B-
-Individual or small group of tumour cells, with
focally desmoplastic or inflamed stroma.
-Lymphovascular Invasion +/-
- Lack of Solid Growth

52. PATTERN C-
-Diffusely infiltrative glands, with extensive
desmoplastic stroma.
-Lymphovascular Invasion +/-
- Solid Growth present.

53. HISTOLOGICAL TYPES OF HPV-ASSOCIATED
ADENOCARCINOMA OF THE UTERINE CERVIX
Usual Type-~75% of all endocervical adenocarcinomas.
-Cells with mucinous cytoplasm constitute only 0–50% of the tumour. Papillary
(including villoglandular) and micropapillary growth can be observed, mimicking
serous carcinoma architecturally but not cytologically.
-Villoglandular variant

54. USUAL TYPE-
Irregular and confluent glands composed
of mucin-depleted cells, which show
indistinct cytoplasm and elongated,
pseudostratified, hyperchromatic nuclei.
Conspicuous apical mitoses and
apoptoses
are present.

55. Villoglandular variant-
Tumour with predominant exophytic
papillary growth. Papillae are lined
by mucin-depleted (usual-type)
epithelium with nuclear
hyperchromasia.

56. Mucinous type- ~10% of all endocervical adenocarcinomas.
-There is intracytoplasmic mucin in ≥ 50% of cells, typically with a minor component of
usual adenocarcinoma. This type is subdivided into the following variants:
1-Mucinous NOS adenocarcinoma
2-Intestinal adenocarcinoma
3-Signet-ring cell adenocarcinoma
4-Stratified mucin-producing carcinoma

57. MUCINOUS NOS-
Irregular glands lined by columnar
mucinous epithelium displaying evident
nuclear hyperchromasia, mitoses, and
apoptoses.

58. s
HPV-associated adenocarcinoma,
mucinous intestinal type
Goblet cell intestinal mucinous
differentiation is noted in an
otherwise usual-type adenocarcinoma.

59. Signet ring cell type-
Poorly differentiated carcinoma featuring
individual infiltrative tumour cells, some with a
central space imparting a signet-ring
appearance. The mucinous nature of the
central vacuole is highlighted by Alcian blue
staining

60. INVASIVE STRATIFIED MUCIN-PRODUCING
TYPE
Invasive proliferation of solid nests in an inflamed
stroma. Tumour nests are composed of
mucinous epithelial cells forming aggregates.

61. Invasive Adenocarcinoma-
A 3D cluster of malignant glandular
cells together with a strip of
adenocarcinoma in situ.

62. ADENOCARCINOMA OF THE UTERINE
CERVIX- HPV INDEPENDENT- GASTRIC TYPE
• 10-15 % of all endocervical adenocarcinoma.
• Can be associated with Peutz –Jeghers Syndrome (germline STK-11 Mutation).
• Pathogenesis- Precursor lesions-Atypical lobular endocervical glandular hyperplasia and
gastric adenocarcinoma in-situ.
• Behaves aggressively and carries poor prognosis as compared to HPV associated
tumours.

63. S
-Infiltrative mucinous glands showing
Nuclear atypia.
-IHC-Positive for MUC 6, PAX-8, CA-IX,
CEA and CK-7.

64. ADENOCARCINOMA OF THE UTERINE
CERVIX- HPV INDEPENDENT- CLEAR CELL
TYPE
-3-4 % of all cervical adenocarcinomas.
-Can be sporadic or in utero DES exposure.
-Tubulocystic, papillary and solid
Architecture lined by clear cells

65. ADENOCARCINOMA OF THE UTERINE
CERVIX- HPV INDEPENDENT- MESONEPHRIC
TYPE -<1 % of cervical adenocarcinomas.
-Associated with mesonephric remnants,
KRAS mutation and gain in chromosome 1q.
-Classic ductal and tubular pattern- with
Eosinophilic secretion as well as focal
Intraluminal debris.

66. OTHER ADENOCARCINOMAS OF THE
UTERINE CERVIX.
• Endometroid Adenocarcinoma (<1%)
• Serous carcinomas secondarily involving cervix.

67. Endometroid Adenocarcinoma of the cervix.
- Well formed glands
- Tumour infiltrating lymphocytes
- HPV and m-RNA ISH –Negative.

68. CARCINOSARCOMA OF THE UTERINE CERVIX
Malignant epithelial and mesenchymal component
Cervical carcinosarcomas can have better
prognosis as many a times they present at an early stage
Usually- IB.

69. ADENOID BASAL CARCINOMA OF THE
UTERINE CERVIX
-BASALOID CELLS WITH CYSTIC CHANGE.
-No chance of metastasis, hence the term
adenoid basal tumour.
-IHC positivity for p-16, p-63 and
cytokeratins.

70. OTHERS
• Carcinoma of the uterine cervix, Unclassifiable
• Adenomyoma of uterine cervix
• Adenosarcoma of uterine cervix
• Germ cell tumour of the uterine cervix- Mature Teratoma, Endodermal Sinus
Tumour, Yolk Sac Tumour, choriocarcinoma.

71. Adenomyoma-
-Mesonephric type and endocervical type
-Occurs as intramural or polypoidal mass.
-Widely spaced glands within smooth muscle–rich
stroma .Some Glands are cystically dilated; others a
arranged in Small lobules. Intraglandular papillary
infoldings are Seen.

72. Adenosarcoma of uterus- 0.16%
Biphasic lesion with a benign, simple epithelial
component lining exophytic
(cauliflower-like, phyllodes-like)
projections of stromal cells
DD- benign endometrial or cervical polyp.

73. NEUROENDOCRINE NEOPLASM OF UTERINE
CERVIX
-Arises from neuroendocrine cells of
Squamous and glandular epithelium.
-Neuroendocrine tumour of cervix Grade1-
Nested pattern, focal glandular formation,
and cells with a moderate amount of
cytoplasm and relatively uniform nuclei.

74. Neuroendocrine Tumour Grade 2
Nested and trabecular patterns, cells
with a moderate amount of cytoplasm,
variable nuclei, and mitotic figures.

75. Small cell Neuroendocrine Carcinoma
This cervical lesion is composed of cells
with hyperchromatic nuclei, scant
cytoplasm, and abundant mitotic activity.
There is nuclear moulding in areas.

76. P-16

77. synaptophysin

78. Large Cell NEC-
This cervical tumour is composed
of cells with prominent nucleoli,
abundant cytoplasm,
and areas of necrosis.

79. Synaptophysin

80. Cervical mixed SCNEC (left) and
adenocarcinoma (right).

81. pTNM staging of cervical cancer (AJCC 8th
edition staging)
• pT Category
___ pT not assigned (cannot be determined based on available pathological information)
___ pT0: No evidence of primary tumor
pT1: Carcinoma is strictly confined to the cervix (extension to the corpus should be disregarded)
pT1a: Invasive carcinoma that can be diagnosed only by microscopy with maximum depth of invasion
less than or equal to 5 mm
___ pT1a1: Measured stromal invasion less than or equal to 3 mm in depth#
___ pT1a2: Measured stromal invasion greater than 3 mm and less than or equal to 5 mm in depth
___ pT1a (subcategory cannot be determined)

82. pT1b: Invasive carcinoma with measured deepest invasion greater than 5 mm (greater than stage IA);
lesion limited to the cervix uteri with size measured by maximum tumor diameter.
___ pT1b1: Invasive carcinoma greater than 5 mm depth of stromal invasion and less than or equal to
2 cm in greatest dimension
___ pT1b2: Invasive carcinoma greater than 2 cm and less than or equal to 4 cm in greatest
dimension
___ pT1b3: Invasive carcinoma greater than 4 cm in greatest dimension
___ pT1b (subcategory cannot be determined)
___ pT1 (subcategory cannot be determined)

83. pT2: Carcinoma invades beyond the uterus, but has not extended onto the lower third of the vagina or
to the pelvic wall
pT2a: Involvement limited to the upper two-thirds of the vagina without parametrial invasion
___ pT2a1: Invasive carcinoma less than or equal to 4 cm in greatest dimension
___ pT2a2: Invasive carcinoma greater than 4 cm in greatest dimension
___ pT2a (subcategory cannot be determined)
___ pT2b: With parametrial invasion but not up to the pelvic wall
___ pT2 (subcategory cannot be determined)

84. pT3: Carcinoma involves the lower third of the vagina and/or extends to the pelvic wall and/or causes
hydronephrosis or nonfunctioning kidney.
___ pT3a: Carcinoma involves lower third of the vagina, with no extension to the pelvic wall
___ pT3b: Extension to the pelvic wall and/or hydronephrosis or nonfunctioning kidney (unless known
to be due to another cause)
___ pT3 (subcategory cannot be determined)
Tumor should involve the mucosal surface.
___ pT4: Carcinoma has involved (biopsy-proven) the mucosa of the bladder or rectum, or has spread
to adjacent organs.

85. pN Category
___ pN not assigned (no nodes submitted or found)
___ pN not assigned (cannot be determined based on available pathological information)
___ pN0: No regional lymph node metastasis
___ pN0(i+): Isolated tumor cells in regional lymph node(s) less than or equal to 0.2 mm, or single cells or clusters of cells
less than or equal to 200 cells in a single lymph node cross section
pN1: Regional lymph node metastasis to pelvic lymph nodes only
___ pN1mi: Regional lymph node metastasis (greater than 0.2 mm but less than or equal to 2.0 mm) to pelvic lymph
nodes
___ pN1a: Regional lymph node metastasis (greater than 2.0 mm diameter) to pelvic lymph nodes
___ pN1 (subcategory cannot be determined)

86. pN2: Regional lymph node metastasis to para-aortic lymph nodes, with or without positive pelvic
lymph nodes
___ pN2mi: Regional lymph node metastasis to para-aortic lymph nodes (greater than 0.2 mm but
less than or equal to 2.0 mm), with or without positive pelvic lymph nodes
___ pN2a: Regional lymph node metastasis to para-aortic lymph nodes (greater than 2.0 mm in
diameter), with or without positive pelvic lymph nodes
___ pN2 (subcategory cannot be determined)

87. pM Category (required only if confirmed pathologically)
___ Not applicable - pM cannot be determined from the submitted specimen(s)
___ pM1: Distant metastasis (includes metastasis to inguinal lymph nodes, intraperitoneal disease,
lung, liver, or bone) (excludes metastasis to pelvic or para-aortic lymph nodes, or vagina). Uterine
serosa and adnexa involvement are considered M1 disease.

88. FIGO Stage (2018 FIGO Cancer Report)
___ I: Carcinoma is strictly confined to the cervix (extension to the uterine corpus should be
disregarded).
___ IA: Invasive cancer identified only microscopically (All gross lesions even with superficial invasion
are stage IB cancers) Invasion is limited to measured stromal invasion with a maximum depth of 5.0
mm#
___ IA1: Measured stromal invasion of 3.0 mm or less in depth.
___ IA2: Measured stromal invasion of more than 3.0 mm and not more than 5.0 mm

89. ___ IB: Invasive carcinoma with measured stromal invasion greater than 5.0 mm (greater than stage
IA) and limited to the uterus###
___ IB1: Invasive carcinoma with measured stromal invasion greater than 5.0 mm and 2 cm or less in
greatest dimension
___ IB2: Invasive carcinoma greater than 2 cm but 4 cm or less in greatest dimension
___ IB3: Invasive carcinoma greater than 4 cm in greatest dimension
___ II: Carcinoma extends beyond the uterus but has not extended onto the pelvic sidewall or to the
lower third of vagina

90. ___ IIA: Carcinoma involves the upper two-thirds of the vagina without parametrial invasion
___ IIA1: Invasive carcinoma 4 cm or less in greatest dimension
___ IIA2: Invasive carcinoma greater than 4 cm in greatest dimension
___ IIB: Parametrial involvement but not involving the pelvic sidewall
___ III: Carcinoma involves the lower third of the vagina and / or extends to the pelvic sidewall and / or
causes hydronephrosis or nonfunctioning kidney and / or involves pelvic and / or para-aortic lymph
nodes
___ IIIA: Involvement of the lower third of the vagina but no extension onto pelvic sidewall
___ IIIB: Extension onto the pelvic sidewall, and / or causing hydronephrosis / nonfunctioning kidney
(unless known to be due to another cause)

91. ___ IIIC: Involvement of pelvic and / or para- aortic lymph nodes (including micrometastases),
irrespective of tumor size and extent (with r and p notations)
___ IIIC1: Pelvic lymph node metastasis only
___ IIIC2: Para- aortic lymph node metastasis
___ IV: Carcinoma extends beyond the true pelvis or involves (biopsy proven) the mucosa of the
bladder and / or rectum (bullous edema is not sufficient) or spread to distant organs
___ IVA: Spread to adjacent organs, i.e., tumor invading the mucosa of the bladder and / or rectum
(biopsy proven) and / or extending beyond the true pelvis (bullous edema is not sufficient)
___ IVB: Spread to distant organs

92. Ancillary Studies-
p16 Immunohistochemistry
___ Positive
___ Negative