1. QA CONFERENCE #2, May 30, 2012
Dr. Esther Ravinsky

2. Case 1 60 year old female Ultrasound guided right breast core biopsy
Palpable nodule, UOQ
Query reactive lymph node
R/O carcinoma
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3. Case 1
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4. Case 1
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5. Case 1
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6. Case 1
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7. Case 1 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
Does not look like invasive ca. Needs immuno
Does not look malignant. Needs immunostains
1 resident
Sclerosing adenosis. Needs IHC to confirm and R/O carcinoma
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
Myofibroblastoma

8. Case 1
Immunohistochemical stain for desmin

9. The answer is: Case 1 Neoplasm with stromal differentiation
Differential diagnosis includes:
Myofibroblastoma with epithelioid features
Metaplastic carcinoma
Sarcoma (e.g. leiomyosarcoma)

10. 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

11. Excision specimen
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12. Excision specimen
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13. Excision specimen
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14. 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

15. 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

16. 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

17. 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

18. Infiltrating myofibroblastoma

19. 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

20. Case 2 65 year old female Endometrial biopsy
History of post menopausal bleeding
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21. Case 2
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22. Case 2
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23. Case 2
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24. Case 2
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25. Case 2
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26. Case 2 DIAGNOSIS Endometrioid adenocarcinoma
Pathologist or resident
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
Adenocarcinoma (illegible) – To Pat

27. Case 2
Immunohistochemical stain for p53

28. Case 2
The answer is:
Serous carcinoma of endometrium

29. Case 3
76 year old female
Endometrial curettage performed at diagnostic hysteroscopy
Post menopausal bleeding
Atypical glandular cells on Pap
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30. Case 3
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31. Case 3
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32. Case 3
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33. Case 3
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34. Case 3
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35. Case 3
Immunohistochemical stain for p53

36. Case 3 DIAGNOSIS Gyne consult Serous carcinoma Pathologist or resident
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
Endometrioid adenocarcinoma. Ignore p53 – To Pat

37. Case 3
Immunohistochemical stain for ER

38. Case 3
The answer is:
Endometrioid adenocarcinoma, FIGO grade 2

39. 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

40. 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

41. 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

42. 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)

43. Differential diagnosis of villoglandular (endometrioid) adenocarcinoma and serous carcinoma of endometrium
Immunohistochemical findings:
Villoglandular/endometrioid carcinoma
The preponderance of grades 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

44. 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
Negative or low level expression
P16
Negative or patchy positivity
Ki-67 index
Extremely high (more than 50-75% of cells)
Less than the index of serous carcinoma

45. Case 4 74 year old female Open cholecystectomy Calculi identified
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46. Case 4
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47. Case 4
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48. Case 4
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49. Case 4
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50. Case 4
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51. Case 4
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52. Case 4
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53. Case 4
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54. Case 4 DIAGNOSIS Pathologist or resident
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
Acute/acute and chronic cholecystitis or benign glandular proliferation
3 Pathologists; 2 ?

55. Case 4 The answer is: Low grade dysplasia High grade dysplasia
Focus suggestive but not diagnostic of invasive adenocarcinoma

56. Case 4 Low grade dysplasia Suggestive of invasive adenocarcinoma
High grade dysplaisa

57. 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

58. Dysplasia of gallbladder
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

59. Dysplasia of gallbladder
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

60. Dysplasia of gallbladder
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

61. Reactive atypia

62. Reactive atypia

63. Reactive atypia

64. Low grade dysplasia

65. High grade dysplasia

66. High grade dysplasia

67. 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

68. 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

69. Well differentiated adenocarcinoma

70. 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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71. Case 5
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72. Case 5
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73. Case 5 DIAGNOSIS Metastatic carcinoma
Pathologist or resident
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

74. 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

75. Case 5
The answer is:
Squamous cell carcinoma

76. 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