qa conference conf #1, may 23, 2012 by dr. e. ravinsky

QA CONFERENCEConf #1, May 23, 2012

By Dr. E. Ravinsky

CASE 1

54 year old female Right breast core biopsy Central calcs R/O DCIS Moderate probability Magnification x 4

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Diagnosis Pathologist or resident

ADH versus florid UDH

CK5/6 immuno will help

1 Pathologist

ADH

Do CK5/6 to rule out UDH

1 Pathologist

ADH (at most) 1 Pathologist

Favour UDH over ADH

Consider CK5/6

1 Resident

Fibrocystic change with florid UDH

Do CK5/6

1 Resident

Florid duct hyperplasia 1 Pathologist

High grade DCIS 1 Pathologist

CASE 1

Immunohistochemistry CK5/6

CASE 1

The answer is:Atypical duct hyperplasia

Case 2

50 year old female Right breast core biopsy Calcs lower aspect R/O DCIS Magnification x 2

Case 2

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Diagnosis Pathologist or Resident

ADH 3 Pathologists

1 Resident

Columnar cell hyperplasia with atypia

1 Pathologist

Low grade DCIS 1Pathologist

High grade DCIS

Suspicious for invasion

1 Resident

Case 2

The answer is:Atypical duct hyperplasia

Atypical Duct Hyperplasia

DEFINITION:A proliferative lesion that fulfills

some, but not all, of the features of duct carcinoma in situ

Diagnosis is based on quantitative and qualitative features

Atypical Duct Hyperplasia

Quantitative features:One duct with qualitative features

of DCISDucts with qualitative features of

DCIS less than 2.0 mm across

Atypical Duct Hyperplasia

Qualitative features: Presence of architectural or cytologic features

of DCIS mixed with features of usual duct hyperplasia

Can have a cribriform or solid pattern Can have cytologic atypia

Nuclear enlargement Nuclear hyperchromasia Irregular chromatin pattern Enlarged pleomorphic nucleoli Atypical cells have distinct cell borders

Atypical Duct Hyperplasia Usual duct hyperplasia

Cellular proliferation has a syncytial appearance because individual cell borders are inconspicuous

May have streaming appearance

Microlumens are irregular in size, irregular in shape (slit-like, ovoid, crescentic, serpeginous)

Cells surrounding lumens are not oriented. Ductal cells tend to be parallel to the lumina

Atypical duct hyperplasia Monomorphic population of cells

with distinct cell borders Can have solid growth pattern Can have cribriform growth pattern

in which microlumens are round Ductal cells are oriented radially

around the lumens In columnar cell hyperplasia with

atypia, cells are columnar Atypia is architectural:

Cribriform Cell bridges Roman arches Micropapillary Radial orientation of nuclei

Atypical Duct Hyperplasia

Usual duct hyperplasia: Cytoplasm may be

reduced, giving the cells an increased nuclear/cytoplasmic ratio, but the nuclei are not enlarged

Cell borders are indistinct Cytoplasm is amphophilic

or weakly eosinophilic and homogenous

Cytoplasm may be vacuolated, but true intracytoplasmic lumens are not identified

Atypical duct hyperplasia: Nuclear enlargement

leading to an increased nuclear/cytoplasmic ratio

Nuclear hyperchromasia and an irregular chromatin pattern

Enlarged, pleomorphic nucleoli

Distinct cell borders May have

intracytoplasmic lumena containing muin

Florid Duct Hyperplasia

Case 3

85 Year female Unguided core biopsy

right breast Probable right breast

cancer Large central mass and

clinically positive node Magnification x 4

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Diagnosis Pathologist or Resident

Poorly differentiated malignancy

Ddx: Poorly differentiated carcinoma;lymphoma; melanoma

Immuno will help

1 Pathologist

Favour poorly differentiated carcinoma

Needs immuno

1 Pathologist

1Resident

Needs immuno 1 Pathologist

1 Resident

High grade invasive duct carcinoma

1 Pathologist

Case 3

Immunohistochemistry for CD45

Case 3

The answer is:Lymphoma breast

Lymphoma Breast

Recognizing lymphoma of the breast can be problematic, particularly in a needle core biopsy

Distinguishing large cell lymphoma from poorly differentiated carcinoma can be difficult.

Large cell lymphoma may assume solid, diffuse and sometimes alveolar growth patterns

Another problem is distinguishing lymphoma from lobular carcinoma

Signet-ring cell lymphoma bears a striking resemblance to signet ring cell lobular carcinoma

Lymphoma Breast

It has been noted, that when a tumour is poorly differentiated, the distinction between poorly differentiated carcinoma and high grade lymphoma cannot be made on H+E examination

The tumour cells in this case are large and monotonous with a very high N/C ratio and scant cytoplasm

The cells of high grade carcinoma tend to be pleomorphic with large vesicular nuclei and prominent nucleoli.

Although they have high N/C ratio, they tend to have more cytoplasm than lymphoma cells

Lymphoma Breast

A reactive lymphocytic infiltrate can be identified in association with lymphomas and carcinomas, but it’s presence together with other features can raise the possibility of lymphoma

This is particularly true for infiltrating lobular carcinomas which tend not to be associated with a lymphocytic infiltrate

In summary, we should be alert to the subtle signs that a breast tumour may be a lymphoma

Immunohistochemistry for cytokeratin and CD45 should be performed in all cases where the morphologic features raise the possibility of lymphoma

Lymphoma Breast

Lymphoma Breast (signet-ring)

Lymphoma Breast

Lymphoma breast (angiocentric)

Solid papillary carcinoma

Solid papillary carcinoma

Case 4

Biopsy vulva 52 year old female Labial lesion R/O VIN Magnification x 2

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Diagnosis Pathologist or Resident

Extramammary Paget disease 1 Pathologist

Paget disease vs melanoma

Needs immuno

2 Residents

2 Pathologists

Paget disease vs melanoma in situ vs squamous cell carcinoma in situ

1 Pathologist

Case 4

The neoplastic cells stain positive on mucicarmine and PAS diastase

Immunohistochemical stain for CEA was done on the biopsy specimen and the neoplastic cells stain positive

Immunohistochemical stains on the excision specimen are positive for CK7 and ER and negative for CK20 and CDX2

Case 4

THE ANSWER IS:Paget disease of vulva

Paget Disease of Vulva

Primary Paget disease (primary cutaneous Paget disease)

Paget disease as an intraepithelial neoplasm/in situ Paget disease

Paget disease as an intraepithelial neoplasm with invasion/invasive primary Paget disease

Paget disease as a manifestation of an underlying cutaneous neoplasm

Secondary Paget disease (Paget disease of non-cutaneous origin)

Paget disease as a manifestation of anal-rectal carcinoma

Paget disease related to other adenocarcinomas

Paget disease as a manifestation of urothelial carcinoma

Staining of Paget disease

Primary Paget disease Paget disease in anal-rectal adenocarcinoma

Paget disease in urothelial carcinoma

CK7+ CK7- CK7+/-

CK20- CK20+ CK20+

CDX2- CDX2+ CDX2+/-

p63- p63- p63+

ER+ ER- ER-

Brst2+ Brst2- Brst2-

Morphology of Paget disease

Paget disease Melanoma VINLocation of tumour cells

Mainly located in the basal and parabasal layers compressing basal keratinocytes. Tumour cells may be present in the upper layers

Located at the dermal-epidermal junction. Tumour cells may be present in the upper layers

Evenly spaced throughout the epidermis singly and in nests

Arrangement of tumour cells

Larger than those of melanoma and have more cytoplasm

May form glandular spaces

Smaller than those of Paget disease and have less cytoplasm

Resemble cells of Paget disease and are large with abundant pale cytoplasm, clear nuclei and prominent nucleoli

PAS + - +

PAS-D + - -

Mucicarmin + - -

Immunohistochemical StainingPrimary Paget Disease Melanoma VIN

Mucin+/- Mucin- Mucin-

CK7+ CK7- CK7+/-

CK20- CK20- CK20-

CEA+ CEA- CEA-

ER+ ER- ER-

Brst2+ Brst2- Brst2-

S100- S100+ S100-

Mart-1- Mart-1+ Mart-1-

HMB45- HMB45+ HMB45-

P63- P63- P63+

P16- P16- P16+

Case 5

25 year old female. ASCUS on recent pap

smear. Colposcopic biopsy of

an erythematous area, Slightly raised, No epithelial changes

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Case 5

Diagnosis Pathologist or Resident

Endometriosis 2 Pathologists

? Endometriosis

Do CD10 (1 pathologist)

2 Pathologists

No malignancy

Edematous stroma with PNMs and tubal metaplasia

1 Resident

Focal moderate squamous dysplasia with stroma a bit hypercellular

1 Resident

Case 5

The answer isEndometriosis of cervix

Endometriosis of cervix Endometriosis of cervix is not uncommon It is usually confined to the superficial third of the

cervical wall They appear as small blue or red nodules on the

cervix Histologically, the glands and stroma resemble

proliferative endometrium The mechanism responsible for the development of

endometriosis is unknown, but it frequently develops following cervical trauma

Cervical endometriosis occurs in 5-43% of patients who have had cautery, cone biopsy or LEEP excisions

Endometriosis of cervix

Endometriosis can be mistaken for AIS The cells of normal proliferating endometrium

are very active They are pseudostratified. They have large

oval nuclei with numerous nucleoli Numerous mitoses are identified

Endometriosis of cervix How to identify endometriosis of cervix:

The glandular cells of endometriosis have an endometriotic appearance with a moderate amount of basophilic cytoplasm and regular oval nuclei

Endometriosis can be recognized by the presence of endometrial-type stroma, but the pathologist must be aware of the possibility or s/he might concentrate on the glands and not notice it

In some cases, there may be abundant hemorrhage and the endometrial-type stroma might not be obvious

The presence of small arterioles like the spiral arterioles can help identify the presence of endometrial-type stroma

CD10 can confirm the endometrioid nature of the stroma

Case 6

37 year old female with 2 ASCUS diagnoses on cervico-vaginal smear

Biopsy cervix taken at colposcopy

Colposcopic impression “?CIN1”

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Case 6

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Case 6

Diagnosis Pathologist or Resident

Atypical endocervical epithelium

? Reactive vs in-situ

Do P16, Ki67

1 Pathologist

Not sure. Some glands at the edge that I would like to explore on deepers

1 Pathologist

ASC-H (one edge of the biopsy)

Favour tubo-endometrial metaplasia (vs endocervical glandular neoplasia/ AIS)

1 Pathologist

Focal discohesive atypical squamous cells

Order serials and deepers1 Pathologist

? Presence of focal high grade squamous dysplasia and tubal metaplasia of endocervical glands

1 Resident

Immature squamous metaplasia 1 Pathologist

Case 6

The answer is:Tubo-endometrioid metaplasia

Tubo-endometrioid metaplasia

Tubo-endometrioid metaplasia of the cervix is the type of metaplasia that is histologically similar to the tubal metaplasia that can develop in the endometrium in patients with unopposed estrogen

The glands are lined by a pseudostratified epithelium composed of columnar cells with a high N/C ratio

Many of the cells are ciliated or have secretory features with apical snouts

The glands lack an associated endometrial stroma Tubo-endometrioid metaplasia occurs commonly

after cervical conization

Tubo-endometrioid metaplasia

Because of the pseudostratification and high N/C ratio, these glands can be misinterpreted as AIS

Tubo-endometrioid or tubal metaplasia should not be misinterpreted as AIS because of the presence of bland nuclei and the absence of significant mitotic activity

Immunohistochemical panels of p16, Ki-67, CEA are used by some in difficult cases

Adenocarcinoma in situ