Practice question answers Pathology of breast II

Practice question answers
Pathology of breast II
© Jun Wang, MD, PhD

1. E. Paget disease of breast is a malignant tumor confined in epidermis and characterized by clusters of large pale tumor cells in epidermis. They are positive for cytokeratin but negative for S-100, a marker for melanocytic differentiation. Contact dermatitis has inflammatory changes but not pale atypical cells in epidermis. Dermatophytosis usually has neutrophilic infiltrate with positive stains for fungal elements. Mycosis fungoides is a cutaneous T cell lymphoma characterized by large atypical T cell in epidermis. These cells are positive for CD4 but not cytokeratin.

2. D. Paget disease of breast is associated underlying breast cancers. Abnormal insulin activity is seen in diabetes, a risk factor for fungal infection. Allergic reaction is the cause for some contact dermatitis. UV light is associated with many skin cancers, but not Paget disease of breast.

3. B. Dilated ducts filled with monotonous cells with cribriform architecture is at least atypical ductal hyperplasia. When more than a few ducts are involved, or the lesion is more than 2 to 3 mm, the proper term is ductal carcinoma in situ. Invasive ductal carcinoma has myoepithelial components lacking ducts with irregular shape and irregular arrangement, suggestive of stromal invasion. Lobular carcinoma in situ is characterized by dilated terminal ducts filled with E-cadherin negative, loosely cohesive cells, without cribriform architecture. Mucinous carcinoma is characterized by clusters of atypical cells floating in mucin pool.

4. A. Ductal carcinoma in situ is positive for E-cadherin, but negative for CK903, a protein that is positive for usual ductal hyperplasia and lobular carcinoma in situ. Her2 and p53 are usually positive in high grade tumors, with markedly pleomorphic tumor cells.

5. B. With the presence of intact myoepithelial layers as highlighted by p63 or CD10, it is not invasive. This is high grade ductal carcinoma in situ. Atypical ductal hyperplasia has cytological features of low grade, but not high grade ductal carcinoma in situ.

6. B. With the presence of intact myoepithelial layers as highlighted by p63 or CD10, it is not invasive. This is a papillary type ductal carcinoma in situ. Atypical ductal hyperplasia is less than 3 mm. Intraductal papilloma is usually single growth. Lobular carcinoma in situ is characterized by dilated terminal ducts filled with E-cadherin negative, loosely cohesive cells.

7. C. Lobular carcinoma in situ is characterized by dilated terminal ducts filled with E-cadherin negative, loosely cohesive cells. They are focally positive for keratin 903. Atypical ductal hyperplasia is positive for E-cadherin. Ductal carcinoma in situ is positive for E-cadherin, but negative for CK903. Medullary carcinoma is characterized by sheets of markedly pleomorphic tumor cells in a background of dense lymphoplasmacytic infiltrate. Usual ductal hyperplasia is positive for E-cadherin.

8. D. Core biopsy finding of classic lobular carcinoma in situ only need follow up. Surgery and radiation therapy are for malignancies. Excisional biopsy is recommended for atypical ductal hyperplasia or intraductal papilloma found in core biopsies, to rule out accompanied malignancies that are not sampled during core biopsy process.

9. C. Invasive ductal carcinoma has ducts with irregular shape and irregular arrangement, suggestive of stromal invasion. These tumor cells are positive for E-cadherin, but negative for TTF-1, a marker for thyroid tissue or lung adenocarcinoma. Atypical ductal hyperplasia and ductal carcinoma in situ have dilated ducts without infiltrating pattern. Invasive lobular carcinoma has E-cadherin negative atypical epithelial cells forming single files in stroma.

10. C. A low-grade invasive ductal carcinoma tend to be ER positive and Her2 negative. Triple negative and Her2 positive ER negative invasive ductal carcinoma tend to have high grade tumor cells with marked cytological atypia.

11. C. Irregular shape and irregular arrangement of ducts in a fibrotic background is suggestive of an invasive adenocarcinoma. In this case, invasive ductal carcinoma. Atypical ductal hyperplasia and ductal carcinoma in situ have dilated ducts without infiltrating pattern. Invasive lobular carcinoma has E-cadherin negative atypical epithelial cells forming single files in stroma. Papillary carcinoma has finger like projects with fibrovascular core covered by atypical ductal cells.

12. B. See discussion in question 10.

13. C. For cancers that are Her2 positive, anti-Her2 therapy, including Herceptin, is an important component of the therapeutic approach.

14. C. Single files of tumor cells are highly suggestive of invasive lobular carcinoma, if no ductal differentiation can be found. Atypical ductal hyperplasia and ductal carcinoma in situ have dilated ducts without infiltrating pattern. Medullary carcinoma is characterized by sheets of markedly pleomorphic tumor cells in a background of dense lymphoplasmacytic infiltrate. Chronic lymphocytic leukemia/small lymphocytic lymphoma may have focal small lymphocytic infiltrate. These malignant lymphocytes are positive for CD45 and CD20, but negative of cytokeratin.

15. B. Mutation of CDH1 is the reason invasive lobular carcinoma is negative for E-cadherin. BRCA1 mutation is seen in basal like carcinoma, including medullary carcinoma. Her2 and p53 mutations are seen in various high grade tumors, with markedly pleomorphic tumor cells. ZAP70 mutation is associated a poor prognosis for chronic lymphocytic leukemia/small lymphocytic lymphoma.

16. D. Acute inflammatory type changes in the presence of mass and biopsy finding of markedly atypical cells in lymphatic channels is consistent with inflammatory carcinoma. Acute mastitis is characterized by neutrophilic infiltration without the presence of tumor and tumor cells. Dermatophytosis and diabetic mastopathy are benign process without atypical tumor cells. Lymphangiosarcoma is characterized by complex vascular growth with atypical endothelial cells.

17. E. Medullary carcinoma is characterized by sheets of markedly pleomorphic tumor cells in a background of dense lymphoplasmacytic infiltrate. Diffuse large B cell lymphoma and follicular lymphoma is positive for CD45 and other lymphocytic markers, but not cytokeratin. Invasive ductal carcinoma has ducts with irregular shape and irregular arrangement, suggestive of stromal invasion. Lymphocytic mastopathy has dense lymphocytic infiltration surrounding normal appearing ducts without atypia, and is associated with diabetes.

18. A. Medullary carcinoma is a basal like breast cancer that is associated with BRCA mutation and negative for ER, PR, and Her2.

19. B. Medullary carcinoma is a basal like breast cancer that is associated with BRCA mutation and negative for ER, PR, and Her2. Bcl2 and MLL2 mutations are seen in certain lymphomas, including follicular lymphoma. CDH1 mutation is seen in lobular carcinoma, either in situ, or invasive. Her2 mutations are seen in various high grade tumors, with markedly pleomorphic tumor cells, but not medullary carcinoma.

20. D. Invasive cancer with fibrovascular core covered by atypical cells is most likely papillary carcinoma. All carcinoma in situ has intact myoepithelial layers. Invasive ductal carcinoma has ducts with irregular shape and irregular arrangement, suggestive of stromal invasion. Invasive lobular carcinoma has E-cadherin negative atypical epithelial cells forming single files in stroma. Zuska’s disease is a periareolar abscess without evidence of malignancy.

21. E. Mucinous carcinoma is characterized by clusters of atypical cells floating in mucin pool. Benign cyst and ductal ectasia have dilated ducts, but not mucin pool, or atypical cells. Ductal carcinoma in situ has dilated ducts and atypical cells, but not mucin pool. Invasive micropapillary carcinoma is characterized by small clusters of tumor cells with halo from surrounding tissue, but not mucin pool.

22. E. Atypical cells with large intracellular vacuole that pushes enlarged nucleus to one end are signet ring cells. When large amount of signet ring cells are present, the tumor is more compatible with signet ring cell carcinoma. Invasive ductal carcinoma has ducts with irregular shape and irregular arrangement, suggestive of stromal invasion. Lobular carcinoma in situ is characterized by dilated terminal ducts filled with E-cadherin negative, loosely cohesive cells, without cribriform architecture. Mucinous carcinoma is characterized by clusters of atypical cells floating in mucin pool. Papillary carcinoma has fibrovascular core covered by atypical cells.

23. B. A well circumscribed tumor with increased fibrous stroma and compressed, stretching ducts without cytological atypia is most likely fibroadenoma. Atypical ductal hyperplasia do not have stromal proliferation. Fibrocystic changes is a group of non-circumscribed pathological processes including stromal fibrosis and cyst formation. Invasive ductal carcinoma has ducts with irregular shape and irregular arrangement. Phyllodes tumor has hypercellular stroma with atypia.

24. D. Phyllodes tumor has hypercellular stroma with atypia. Fibroadenoma does not have hypercellular stroma. Fibrocystic changes is a group of non-circumscribed pathological processes including stromal fibrosis and cyst formation. Papillary carcinoma has fibrovascular core covered by atypical cells. Usual ductal hyperplasia has increased layers of ductal epithelial cells, but not stromal proliferation.



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