KUSUMA CHINAROONCHAI25 Feb 2014

BACKGROUND

Anal squamous cell carcinoma is rare

Risk is HPV infection >> anal intraepithelial neoplasia (AIN)

Problem in diagnosis of small tissue biopsy specimen and anal gland involvement (AIN vs invasive)

Cytokeratin17 (CK17)is a basal/myoepithelial cell keratin induced in activated keratinocytes and associated with disease progression in SCC of uterine, cervix, esophagus, and oral cavity.

MATERIAL & METHODS

Cases 2009-2012 diagnosis of anal SCC, basaloid SCC(BSCC) ,pure basaloid carcinoma and AIN

Files of the James Homer Wright Pathology Laboratories of the Massachusetts General Hospital, Boston, MA and of Brighamand Women’s Hospital, Boston, MA

MATERIAL & METHODS

BSCC: SCC with keratinization and basaloid features (ie, peripheral palisading, smalls cell without distinct intercellular bridges, and retraction artifact)

Pure BSCC: a tumour with basaloid features lacking keratinzination or other features typical of SCC with morphologic likeness to cutaneous basal cell carcinomas)

HPV status from in situ hybridization, polymerase chain reaction testing, p16INK4a immunohistochemistry and previous reports

IMMUNOHISTOCHEMISTRY

5 mm thick sections of formalin-fixed paraffin-embedded tissue

primary antibodies against CK17 (cloneE3, 1:50, Dako, Carpinteria, CA)

Studies staining

Negative VS positive

Pattern of staining expression

IMMUNOHISTOCHEMISTRY

Positive staining

Peripheral/rim (basal or outer 1/3)

Diffuse (basal and Up)

Negative staining

Absence

Surface/center (suprabasal or inner 2/3)

< 10% of basal cells

STATISTICAL ANALYSIS

Sensitivity

Specificity

Positive predictive value (PPV)

Negative predictive value (NPV)

Fisher’s exact test

Significant P-value < 0.05

RESULTS

33 cases from 27 patients

12 typical SCCs (2 papillary architecture)

8 invasive BSCCs

2 invasive pure BSCCs

11 AIN

6 patients (5 SCCs + 1 BSCC) concurrent with AIN

RESULTS

24 (92%) HPV positive

100% (20/20) of invasive SCCs and BSCCs >> +ve CK17 stain

92% (11/12) in invasive SCCs >> diffuse staining (1/12 peripheral staining)

75% (6/8) in BSCCs >> diffuse staining (2/8 peripheral staining)

RESULTS

Diffuse positive CK 17 in each histologic pattern

83% (10/12) Infiltrative pattern of invasion in SCCs and BSCCs

86% (7/8) Blunt-type invasion

2 pure BSCCs negative for CK17, positive for p16

RESULTS

45% (5/11) AIN surface CK17 staining (Grade3/high grade dysplasia)

1/11 AIN focal peripheral staining in worrisome area of invasion in H&E stain

5/11 AIN negative CK17

6 invasive + AIN

5 diffuse CK17 in invasive lesion

1 Positive CK17 in both AIN and invasive lesion

SCCS & DIFFUSE CK17

BSCCS & DIFFUSE CK17

PURE BSCCS & -VE CK17 & P16

AIN 3 & SURFACE CK17

AIN 3 & DIFFUSE CK17

AIN 3 WITH SUSPECTED EARLY INVASION & BASAL CK17

SCCS + AIN 3 & CK17 PATTERN

NORMAL SQUAMOUS EPITHELIUM & CK17

RESULTS

DISCUSSIONS

AIN 1 or low grade dysplasia: lower 1/3 epithelium >> topical agents treatment as imiquimod

AIN 2 or 3 or high grade dysplasia: 2/3 or all epithelium >> excision

DISCUSSIONS

Problem in anal biopsy specimen

Presence vs absence AIN

Degree of dysplasia

***Presence vs absence invasive carcinoma***

Small pieces and poorly oriented

Cell extended to anal gland

Inflammation cell infiltrate

DISCUSSIONS

Insitu lesion >> local excision

Invasive lesion >> excision plus CMT & RT

Previous studies report increased expression of CK17 in SCCs when compared with normal adjacent tissue in cervix, oral cavity, larynx, esophagus and lung. (Ikeda et al, Kitamura et al, Purkis et al and Chu and Weiss.)

DISCUSSIONS

Williams et al showed that CK17 is expressed in basal cells of the normal epithelium of the distal anal canal and perianal skin, but in our laboratory CK17 staining was not seen in the normal squamous epithelium of the anal canal or perianal skin.

A potential pitfall in the utility of CK17 is that the rare pure basaloid variant of anal carcinoma is negative for CK17.

P16 positive in the rare pure basaloid variant of anal carcinoma may reflect pathogenesis process.

FOR YOUR ATTENTION

“THANK YOU.”