qa conference #2, may 30, 2012 dr. esther ravinsky

QA CONFERENCE#2, May 30, 2012

Dr. Esther Ravinsky

Case 1

60 year old female Ultrasound guided right

breast core biopsy Palpable nodule, UOQ Query reactive lymph

node R/O carcinoma Magnification x 2

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DIAGNOSIS Pathologist or resident

Mammary carcinoma pending stains. There is some spindling ?metaplastic ca

1 pathologist

Probably invasive carcinoma. Need immunostains 1 resident; 1pathologist

Epithelioid and spindled neoplasm. Do testing 1 pathologist

Does not look like invasive ca. Needs immuno 1 pathologist

Does not look malignant. Needs immunostains 1 resident

Sclerosing adenosis. Needs IHC to confirm and R/O carcinoma

1 resident

Infiltrative tumour. Needs IHC (possibly myoepithelial, possibly metastatic possibly invasive carcinoma)

2 pathologists

Spindle cell neoplasm Do IHC (?myofibroblastoma) 1

Myofibroblastoma vs granular cell tumour 1

Myofibroblastoma 1

Case 1

Immunohistochemical stain for desmin

Case 1

The answer is:Neoplasm with stromal

differentiation Differential diagnosis includes:

Myofibroblastoma with epithelioid features Metaplastic carcinoma Sarcoma (e.g. leiomyosarcoma)

Case 1

Mastectomy was performed The nodule which had been biopsied was

described as a pinkish-grey encapsulated nodule ?lymph node ?tumour nodule, 1.8 cm in dimension

Excision specimen

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Excision specimen

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Myofibroblastoma

Rare benign breast tumour arising from myofibroblasts

Radiologically, the tumours are homogeneous, lobulated, well circumscribed and lack microcalcifications

The excised mass is firm and rubbery with a lobulated external surface

The cut surface consists of homogeneous, bulging, gray to pink whorled tissue

Myofibroblastoma

Microscopically, the classic type of myofibroblastoma is devoid of mammary ducts and lobules, with compressed breast parenchyma forming a peripheral pseudocapsule

The tumour consists of bundles of slender bipolar uniform spindle shaped cells typically arranged in clusters which are separated by broad bands of hyalinized collagen distributed throughout the tumour

In a minority of cases, fat cells are present in the tumour, reflecting invasion of the surrounding tissue

Myofibroblastoma, variant forms

The epithelioid variant features polygonal or epithelioid cells arranged in alveolar groups

Epithelioid cells may be mixed with more classical variants or they can constitute the predominant growth pattern

Because of the epithelioid growth pattern, the tumour may be mistaken for an infiltrating lobular carcinoma, especially in the limited material of a needle core biopsy

Other variants which may be mistaken for malignancy are the cellular variant, the infiltrative variant and the deciduoid variant

Myofibroblastoma, variant forms

By immunohistochemistry, myofibroblastomas stain positive for actin and desmin and negative for cytokeratin

Noticing a spindle cell component can raise a red flag for the pathologist considering a diagnosis of carcinoma and result in the ordering of appropriate immunohistochemistry

The absence of mitotic figures should raise a red flag if the diagnosis of metaplastic carcinoma or sarcoma is considered

Infiltrating myofibroblastoma

Myofibroblastoma

No recurrences have been reported after follow-up of 3 to 126 months

Excision with wide margins is recommended when myofibroblastoma is identified in a needle core biopsy

Case 2

65 year old female Endometrial biopsy History of post

menopausal bleeding Magnification x 4

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Endometrioid adenocarcinoma 1 pathologist; 2 ?

Endometrioid adenocarcinoma in a background of complex hyperplasia with atypia

1 pathologist

Complex hyperplasia with atypia 1 resident; 1?

High grade: Serous papillary carcinoma vs. endometrioid adenocarcinoma FIGO 2. Do p53 and deepers to R/O MMMT

2 pathologists;1 resident

Endometrioid adenoca with focal serous features. Do p53; Serous carcinoma

1 pathologist; 1 resident

Endometrioid carcinoma with area showing high grade nuclei. Do p53 to R/O serous carcinoma

1 pathologist

Adenocarcinoma (illegible) – To Pat 1 pathologist

Case 2

Immunohistochemical stain for p53

Case 2

The answer is:Serous carcinoma of endometrium

Case 3

76 year old female Endometrial curettage

performed at diagnostic hysteroscopy

Post menopausal bleeding

Atypical glandular cells on Pap

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Immunohistochemical stain for p53

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Gyne consult 1 pathologist

Serous carcinoma 2 pathologists: 1 resident 2 ?

High grade endometrioid adenocarcinoma vs. serous carcinoma.

3 pathologists; 1 resident; 1 ?

Moderately differentiated endometrial adenocarcinoma

1 resident

Endometrioid adenocarcinoma;

p53 expression – not over-expressed

1 pathologist

Endometrioid adenocarcinoma. Ignore p53 – To Pat

1 pathologist

Case 3

Immunohistochemical stain for ER

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The answer is: Endometrioid adenocarcinoma,

FIGO grade 2

Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium

Serous carcinoma It is defined by a discordance between its architecture

which appears well differentiated; papillary or glandular and its nuclear morphology which is high grade

Papillary architecture is complex with short thick papillae though thin papillae may also be present.

The cells covering the papillae and lining the glands form small papillary tufts, many of which are detached and float freely in spaces between the papillae and in the gland lumens

Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium The cells are cuboidal or hobnail shaped and

contain abundant epsinophilic cytoplasm The cells tend to be loosely cohesive The cells show marked cytologic atypia with

marked nuclear pleomorphism, hyperchromasia and macronucleoli

Multonucleated cells, giant nuclei and bizarre forms can occur

Mitotic activity is high and abnormal mitotic figures are easily identified

Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium Villoglandular carcinoma is characterized by the

presence of long delicate papillary fronds that do not show papillary tufting

The cells are columnar, resembling the cells in endometrioid adenocarcinoma

The glands in endometrioid adenocarcinoma have a smooth luminal border and are lined by columnar cells with nuclei which are grade 1 or 2.

Endometrioid adenocarcinomas with grade 3 nuclei are almost always solid

Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium Immunohistochemical findings:

Serous carcinoma 75% of serous carcinomas are strongly and diffusely

positive for p53 The typical serous carcinoma lacks diffuse ER and PR

expression. Carcinomas with hybrid endometrioid/serous features and

admixtures of endometrioid and serous components can express ER

Diffuse strong p16 staining is characteristic of serous carcinomas

The Ki67 labelling index is extremely high (50%-75% of tumour nuclei)

Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium Immunohistochemical findings:

Villoglandular/endometrioid carcinoma The preponderance of grades 1 + 2 and half of the

grade 3 endometrioid carcinomas strongly express ER and PR

P53 expression is not identified in FIGO 1 carcinomas. It is identified in a minority of FIGO 2 carcinomas and in a significant number of FIGO 3 carcinomas

However, when p53 staining is prominent, serous carcinoma, clear cell carcinoma or undifferentiated carcinoma should be considered

Overexpression characteristic of serous carcinoma is defined as diffuse and strong expression in more than 50-75% of tumour cells

Low-grade expression of p53 in less than 50% of tumour cells is commonly found in endometrioid carcinomas

Endometrioid carcinoma can show patchy expression of p16

Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium

Immuno stain Serous carcinoma Endometrioid carcinoma, grades 1 + 2

ER/PR Weakly positive or negative

Strongly and diffusely positive

P53 Strongly and diffusely positive

Negative or low level expression

P16 Strongly and diffusely positive

Negative or patchy positivity

Ki-67 index Extremely high (more than 50-75% of cells)

Less than the index of serous carcinoma

Case 4

74 year old female Open cholecystectomy Calculi identified Magnification x 2

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Suspicious for adenocarcinoma. Lining epithelium dysplastic. Small irregular glands in deeper tissue

1 Pathologist

Suspicious for malignancy 1 Resident

Adenocarcinoma or invasive adenocarcinoma

1 Pathologist; 1 ?

Severely dysplastic glandular cells. Suspicious for invasion ?invasion

1 pathologist; 1Resident

Gastric/intestinal metaplasia. Adenocarcinoma in situ

1 Resident

Acute/acute and chronic cholecystitis or benign glandular proliferation

3 Pathologists; 2 ?

Case 4

The answer is:Low grade dysplasiaHigh grade dysplasiaFocus suggestive but not

diagnostic of invasive adenocarcinoma

Case 4

Low grade dysplasia

High grade dysplaisaSuggestive of invasive adenocarcinoma

Dysplasia of gallbladder

Dysplastic changes, mostly low-grade have been reported as an incidental finding in 1% to 3.5% of cholecystectomies

This frequency varies significantly between patient populations and generally parallels the incidence of adenocarcinoma

Dysplasia is detected in 40%-50% of adenocarcinomas

Most patients with high grade dysplasia have associated invasive carcinoma


Dysplasia of gallbladder is characterized by a disorderly proliferation of atypical columnar or cuboidal cells

Low-grade dysplasia shows cells with mild stratification and nuclear enlargement with only minimal nuclear enlargement

High grade dysplasia shows marked nuclear enlargement and irregularity, hyperchromasia and significant loss of polarity

Prominent tufting of of irregularly shaped nuclei and apoptosis are also characteristic of high-grade dysplasia

An abrupt transition from abnormal to normal epithelium is characteristic of both grades of dysplasia


The differential diagnosis of dysplasia is marked reactive/degenerative changes

Biliary epithelium has the capacity to develop marked cytologic atypia secondary to injury which, at times, may be difficult to distinguish from true neoplastic changes

Also, neoplastic transformation is often related to chronic inflammatory conditions


Lesions that show marked nuclear stratification, enlargement, hyperchromasia, and irregularity in the absence of inflammation or ulceration favour dysplasia, especially high-grade

Reactive atypia does not show all of these features at once

Reactive epithelium often shows a peculiar moulding pattern of the cells and reveals maturation towards the surface of the epithelium

Nuclear polarity is usually maintained in reactive epithelium

One should be cautious about making a definative diagnosis of dysplasia in areas of acute inflammation or ulceration

Reactive atypia

Low grade dysplasia

High grade dysplasia

Differential diagnosis of invasive adenocarcinoma and reactive changes There are difficulties in distinguishing the cytologic

changes of invasive adenocarcinoma from reactive changes Carcinoma cells may be deceptively bland and

regenerative cells may show a marked degree of atypia

At the architectural level: Well differentiated adenocarcinoma often have well

organized gland formation which may be difficult to distinguish from Rokitansky-Aschoff sinuses or Luschka’s ducts (Benign biliary-type ducts commonly present in the perimuscular tissue at the hepatic surface of the gallbladder

Differential diagnosis of invasive adenocarcinoma and reactive changes Lushka’s ducts are composed of uniform, evenly sized tubules,

all arranged parallel to the surface Rokitansky-Aschoff sinuses are continuous, oriented

perpendicularly to the mucosa, show undulating contours and may appear flask-shaped

Invasive adenocarcinoma consists of smaller and more variably sized glands arranged in a haphazard fashion

Malignant glands have open round lumina and angulated contours and are more densely packed

Nuclear enlargement, nuclear irregularity, hyperchromasia, loss of polarity, apoptotic cells, intraglandular necrosis with neutrophils, open lumina, perineural or vascular invasion are in favour of carcinoma when present

Subtle nuclear grooves can be helpful in recognizing an extremely well differentiated adenocarcinoma

Well differentiated adenocarcinoma

Case 5

71 year old female Core biopsy cervical lymph

node left neck Patient had lumpectomy for

infiltrating duct carcinoma in 2010

FNAB had been performed and showed malignant cells with no cellular material available for ancillary techniques

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Squamous cell carcinoma/ favour squamous cell carcinoma/ ?squamous cell carcinoma (do immunos)

2 Pathologists; 2 ?

Positive for carcinoma. Poorly differentiated carcinoma, DDX: Metastatic IDC vs. other primary

1 pathologist; 1 Resident

Metastatic carcinoma 1 ?

Carcinoma. Will do ER, PR, CK7, CK20 1 Pathologist;1 Resident

High grade non-lymphoid malignancy. Do immunos

2 Pathologists

Malignant. Needs immuno 1 Resident

Adenoca c/w ductal ca, pending stains 1 Pathologist

Case 5

Immunohistochemistry was performed and the tumour cells stained positive for P63 and negative for ER and Brst2

The report of the previous breast carcinoma was reviewed and was a low grade infiltrating duct carcinoma which was strongly ER positive

Case 5

The answer is:Squamous cell carcinoma

Case 5

Patient subsequently had a total thyroidectomy and left modified radical neck dissection

Thyroid masses: Papillary carcinoma, tall cell variant, with

extrathyroidal extension into muscle. Cervical lymph nodes:

Metastatic papillary carcinoma to several lymph nodes.

Matted together lymph nodes in neck: Anaplastic (undifferentiated) thyroid carcinoma,

epithelioid pattern, with tumor giant cells and stromal eosinophilia associated with tall cell papillary carcinoma with extra-nodal extension

Part of the undifferentiated component appeared squamoid

qa conference #2, may 30, 2012 dr. esther ravinsky

Documents

desmin slide

leiomyosarcoma slide

dimension slide

deciduoid variant slide

surrounding tissue slide

esther ravinsky slide

pathologist epithelioid

tumour nodule