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Avances en patología
ginecológica (1)
Jaume Ordi
Hospital Clinic
Barcelona
Clinton L, Miyzazaki K, Ayabe KA, Davis J, Tauchi-Nishi P,
Shimizu D, Burns JA
School of Medicine, Honolulu, HI, Queen’s Medical Center,
Honolulu, HI, USA
The LAST guidelines in clinical
practice: community experience
of implementing
recommendations for p16 use
- 3 -
• A two tiered standardized terminology (LSIL and HSIL)
has been proposed (LAST project) to be used for all
HPV+ squamous precursors of the lower anogenital tract
• In this system the use of p16 is recommended:
1. To differentiate HSIL from benign mimickers
2. To establish a diagnosis of CIN2-3 in case of doubt with CIN1
3. In case of professional disagreement
4. Biopsies with ≤CIN1 in women with Pap smears showing ≥HSIL
LAST guidelines in
clinical practice: Background
- 4 -
• To compare p16 use before and after implementation of
the LAST guidelines
• To assess the increase in HSIL diagnosis attributable to
the new guidelines
• Review of all cervical biopsies diagnosed by two
pathologists for 1 year prior to and after the adoption of
the LAST guidelines
LAST guidelines in
clinical practice: Aims and methods
- 5 -
LAST guidelines in
clinical practice: Results
Before LAST After LAST P-value
P16 use rate 2.8% 4.9% .0009
P16 use category
1. HSIL vs mimic 94.1% 47.1% <.0001
2. CIN1 vs. CIN2 5.9% 27.1% .0024
3. Professional disagreement 0% 0% N/A
4. High - risk Pap 0% 25.9% .005
Before LAST After LAST P-value
10.8% 17.9% .0287
HSIL biopsies detected with p16
- 6 -
• Implementation of the p16 LAST guidelines resulted in
a significant increase in p16 use, but much lower
than the 20% predicted
• The increase was largely due to increase in categories
CIN1 vs CIN2 and previous/concurrent high-grade Pap
• A significant number of cases would have been
underdiagnosed without implementation of the LAST
guidelines
LAST guidelines in
clinical practice: Conclusions
Mehta R, Khurana KK.
SUNNY Upstate Medical University Syracuse NY, USA
Anal cytology as a predictor of
anal intraepithelial neoplasia: an
institutional experience
- 8 -
• The role of anal cytology in early detection of anal cancer
is still evolving
• There are no accepted guidelines for epithelial cell
abnormality in anal cytology smears
• The purpose of the study was to evaluate whether anal
cytology is valuable screening test for identifying
anal intraepithelial neoplasia (AIN)
Anal cytology as a
predictor of AIN: Background, aims
- 9 -
• Review of anal smears from a two year period. All
smears with follow-up biopsies within a 6 month
period were identified
• Anal cytology smears classified according to the
Bethesda 2001 classification
• Sensitivity for AIN and correlation between cytologic
and histologic grade of dysplasia were calculated
Anal cytology as a
predictor of AIN: Methods
- 10 -
Biopsy diagnosis
Cytology diagnosis N Negative LG-AIN HG-AIN2 HG-AIN3
Negative 4 1 1 2 0
ASC-US 21 7 12 2 0
LSIL 33 7 12 6 8
HSIL 17 6 4 4 3
Anal cytology as a
predictor of AIN: Results
- 11 -
• Histological grade of dysplasia may be underestimated
by anal cytology
• High rate of detection of high grade dysplasia following a
LSIL cytology is supportive of high resolution anoscopy
and biopsy for management of anal cytology with LSIL
interpretation
Anal cytology as a
predictor of AIN: Conclusions
Jeffus SK, Gehlot A, Holthoff A, Stone R, Post S, Quick CM.
UAMS, Little Rock, AR. USA
Histologic predictors of clinical
outcome in vulvar squamous cell
carcinoma: a study of 145 cases
- 13 -
• To identify histologic patterns of invasive vSCC and
associated stromal tumor response correlate with clinical
outcome
Predictors of clinical
outcome in vSCC: Aims
- 14 -
• 145 consecutive cases of vulvar squamous cell
carcinomas (vSCC)
• Patterns of invasion classified as infiltrative or
nested/pushing
• Stromal response was documented as fibromyxoid
tumor response (myxoid stroma surrounding the tumor)
or prominent band-like lymphoid tumor response
(identified at low power magnification)
Predictors of clinical
outcome in vSCC: Methods
- 15 -
• 43% of the tumors had an infiltrative pattern of invasion
and 57% a nested/pushing pattern
• 46% had a fibromyxoid tumor response and 38% a
lymphoid tumor response
• Infiltrative pattern correlated with fibromyxoid
stroma, greater depth of invasion and recurrence (41%
vs 21%, p=0.0458)
Predictors of clinical
outcome in vSCC: Results
- 16 -
• Infiltrative pattern and fibromyxoid stromal response
are associated with worse prognosis in patients
with vSCC, whereas nested/pushing and inflammatory
response are associated with better outcomes
• These features should be recognized and reported
and may help to plan more efficiently therapeutic
protocols
Predictors of clinical
outcome in vSCC: Conclusions
Ordi J, Rodríguez-Carunchio L, Soveral I, Torné A, Pahisa J,
Marimon L, del Pino M.
Department of Pathology, Hospital Clinic, Barcelona
HPV Negative Carcinoma of the
Uterine Cervix: a Biologically
Distinct Type of Cervical Cancer
with Poor Prognosis
- 18 -
• To analyze with highly sensitive PCR techniques CC
testing negative for HPV by HC2
• To determine the clinico-pathological characteristics
of those patients with tumors with confirmed HPV-
negativity
HPV negative
Carcinoma of the cervix: Aims
- 19 -
• All women (n=136) having a HPV testing performed by
HC2 either simultaneously or within 6 months before the
histological diagnosis
• FFPE tumor samples from all negative cases were
reanalyzed and genotyped for HPV using three
different PCR assays (SPF10, GP5+/6+ and E7
specific assay)
• p16 expression was evaluated by IHC in all cases
HPV negative
Carcinoma of the cervix: Methods
- 20 -
HPV negative
Carcinoma of the cervix: Results (1) Table 2. Histological type, viral load by hybrid capture 2 testing, SPF10 PCR, GP 5+/6+ PCR and E7 specific PCR results and 1 immunohistochemical staining for p16INK4a in Hybrid Capture 2-negative cervical cancers. 2 3
Patient Histological type HC2 (RLU) PCR HPV
SPF10
PCR HPV
GP5+/6+
PCR HPV
E7
p16INK4a
1 ADC, mucinous 0.59 16 16 Positive -
2 ADC, mucinous 0.50 18 18 Positive -
3 SCC, non-keratinizing 0.35 16 16 Positive +
4 SCC, keratinizing 0.81 45 45 Positive +
5 SCC, non-keratinizing 0.85 Negative 68 Positive +
6 SCC, non-keratinizing 0.11 11 Negative Negative * +
7 ADC, mucinous 0.18 Negative Negative Negative - (+ focal)
8 ADC, mucinous 0.15 Negative Negative Negative +
9 ADC, mucinous 0.23 Negative Negative Negative -
10 ADC, mucinous 0.14 Negative Negative Negative - (+ focal)
11 SCC, keratinizing 0.50 Negative Negative Negative -
12 SCC, non-keratinizing 0.13 Negative Negative Negative -
13 SCC, non-keratinizing 0.29 Negative Negative Negative +
14 Adenosquamous
carcinoma
0.27 Negative Negative Negative - (+ focal)
HC2: Hybrid capture 2; RLU: relative light units; *: the probe did not include the oligonucleotides for HPV114
- 21 -
HPV negative
Carcinoma of the cervix: Results (2)
HPV negative
Carcinoma of the cervix: Results (3)
- 23 -
• HC2-negative result is an uncommon finding in women
with CC. Almost ½ of these cases contain HPV types
included in HC2 test
• p16 IHC might not always be a reliable marker of the
presence of HPV
• HPV-negativity is more frequent in adenocarcinomas
is associated with poor prognosis
HPV negative carcinoma
of the cervix: Conclusions
Ordi J, Castillo P, del Pino M, Ordi O, Rodríguez-Carunchio L,
Millan R, Garcia C, Ramírez J.
Department of Pathology, Hospital Clinic, Barcelona
Whole-Slide Imaging in the
Routine Diagnosis in
Gynecological Pathology
- 24 -
- 25 -
• To determine the accuracy of interpretation using WSI
in the routine diagnosis of gynecological specimens as
compared with conventional light microscopy (CLM)
• To understand the technology limits and possible
interpretative pitfalls
Routine WSI Diagnosis
in GYN Pathology: Aims
- 26 -
• All gynecological biopsies (including small biopsies and
surgical specimens) received at the department of
pathology of the Hospital Clinic of Barcelona in July 2013
• Analyzed blindly by two gynecological pathologists
• One of them performed the diagnosis using CLM
(gold standard)
• The second using WSI. (H&E slides were digitized
in a Ventana iScan HT, Roche diagnostics at 20x)
Routine WSI Diagnosis
in GYN Pathology: Methods (1)
- 27 -
• The discrepancies were classified according to a
modified Goldman classification
• Major (significant differences in clinical management or
benign vs. malignant)
• Minor (no or minor clinical relevance)
• Weighted Kappa statistics for two observations
• Time spent by the technicians to charge the scanner
and review the scanning process, and percentage of
rescanning were also evaluated
Routine WSI Diagnosis
in GYN Pathology: Methods (2)
- 28 -
• 351 cases, consisting of 966 glass slides, were evaluated
• 48.4% normal or reactive lesions
• 23.4% benign tumors
• 4.3% low-grade premalignant lesions
• 11.7% high-grade premalignant lesions
• 10.0% malignant tumors
Routine WSI Diagnosis
in GYN Pathology: Results (1)
- 29 -
• Complete agreement between WSI and CLM
interpretations was observed in 93.7% of the biopsies
• Major discrepancies were observed in 7 cases (2%)
• 6 underdiagnosed or missed small high grade squamous
intraepithelial lesions of the cervix
• 1 lymph node micrometastasis of an ovarian carcinoma
missed in the WSI evaluation.
• Minor discrepancies accounted for 4.3% biopsies
Routine WSI Diagnosis
in GYN Pathology: Results (2)
- 30 -
• Inter-observer agreement for WSI and CLM
evaluations was at the almost perfect level (kappa value
0.904; 95%CI: 0.863-0.945)
• Mean time spent by the technician in charging and
removing the slides from the scanner and verifying the
adequacy of the scanning process was 25 seconds per
slide.
• The percentage of slides requiring rescanning was
4.16% and the rate of scanning failure was 0.61%
Routine WSI Diagnosis
in GYN Pathology: Results (3)
- 31 -
Routine WSI Diagnosis
in GYN Pathology: Results (4)
- 32 -
• Diagnosis of gynecological specimens by
WSI is accurate
• Routine diagnosis and digital archiving of
gynecological specimens by WSI may be
introduced in departments of pathology
Routine WSI Diagnosis
in GYN Pathology: Conclusions