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

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• 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

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• 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

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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

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• 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

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• 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

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• 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

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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

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• 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

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• To identify histologic patterns of invasive vSCC and

associated stromal tumor response correlate with clinical

outcome

Predictors of clinical

outcome in vSCC: Aims

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• 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

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• 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

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• 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

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• 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

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• 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

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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

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HPV negative

Carcinoma of the cervix: Results (2)

HPV negative

Carcinoma of the cervix: Results (3)

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• 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

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• 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

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• 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)

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• 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)

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• 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)

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• 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)

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• 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)

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Routine WSI Diagnosis

in GYN Pathology: Results (4)

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• 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