Breast lumps pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shadan Mehraban, M.D.[2]

Overview

Breast development is influenced by different hormones such as estrogen, progesterone, prolactin, and estradiol. The pathophysiology of breast lumps depends on the histological subtypes. Histological findings of breast lumps are different from each other which lead to diagnosis. It is thought that breast lumps are the result of hormonal events and genetic mutations. Estrogen and progesterone may increase risk of benign proliferative disease to 74% and benign breast lesion in post-menopausal women receiving estrogen with or without progesteron for more than 8 years raise by 1.7 fold. Gene mutations are classified into 3 categories based on cancer risk such as BRCA1, BRCA2, TP53 considered as high risk mutations, Homozygous ataxia-telangiectasia, somatic mutation in CHEK2, BRIP1, PALB2 moderate risk mutations, and low risk genes mutation are not determined yet.

Pathophysiology

Physiology

Histological changes of breast

Histological changes of breast undergo continuous changes throughout the life:[4]

  • Fibrocystic disease
    • Histological apperance change from predominance of ducts, lobules to fibrous change, and cyst formation
    • Fibrocystic changes are not associated with breast cancer
  • Diagnostic subtypes and histologic subtypes are described according to their relative risk for cancer as below:[7]
Diagnostic Subtypes
Diagnostic subtypes Breast cancer relative risk
Non-proliferative disease 1.17
Proliferative disease without atypia 1.76
Benign breast disease 2.07
Atypical hyperplasia 3.93
Histologic Subtypes
Histological subtypes Breast cancer relative risk
Adenosis 2.00
Atypical ductal hyperplasia 3.28
Atypical lobular hyperplasia 3.92
Cysts 1.55
Fibroadenoma 1.41
Papilloma 2.06
Histological findings of breast lumps
Breast lumps Histological findings
Atypical hyperplasia[8]
  • Clonal neoplastic proliferations is present.
Atypical ductal hyperplasia (ADH)[9]
  • Localized intraductal proliferations,having some microscopic features of ductal carcinoma in situ (DCIS), usually associated with calcification, duct spaces consist of complex proliferation of monotonous luminal-type cells by creating bridging feature.
  • Differentiation of ADH from DCIS : ADH has less cytological atypia than DCIS.
  • Distribution in severe ADH is restricted to less than 3 contiguous ducts and less than 0.2 cm in size.
Lobular neoplasia[10]
  • Associated to decrease expression or missing expression of E-cadherine, lobular neoplasia is considered to be as incidental findings in during microcalcification evaluation.
Atypical lobular hyperplasia (ALH)[11]
  • ALH is containing monomorphic cells and distend into lobular acini and adjacent terminal ducts.
  • Differentiation between ALH and lobular carcinoma in situ (LCIS) associated with quantitative degrees about lobules and architecture feature.
Apocrine proliferative lesions[12]
  • Apocrine atypia is described by a 3-fold variation in nuclear size or by cribriform structures with nuclear atypia, associated with sclerosing adenosis or complex sclerosing lesion.
Columnar cell lesions (CCL)[13]
  • CCL has heterogeneous set of lesions distinguished by reduplication and microcystic changes in lobular acini, elevated estrogen receptor expression, increased proliferative rate, associated with sclerosing adenosis, clacification and pleomorphic appearnace.
Papillary lesions[14]
  • Arborescent fibrovascular stalk lined to the myoepithelium are present.
Radical scars and complex sclerosing lesions[15]
  • Radial scars are tumor like lesions with stellate nidus of dense elastotic collagen, surrounding with epithelial elements and sclerosing adenosis.
  • Complex sclerosing lesions are kind of radial scars larger than 1 cm which has distorted glandular tissue.
Fibroadenoma[16]
Phyllodes tumor[17]
Pseudoangiomatous Stromal Hyperplasia[18]
Sclerosing adenosis[19]

Pathogenesis

Genetics

Associated Conditions

  • There are no other associated conditions with breast lumps.

Gross pathology

Histopathologic image of fibroadenoma source:Netha Hussain , from Wikimedia Commons
  • Human breast tissue with a stellate area of cancer 2cm in diameter. The lesion could be felt clinically as a hard mobile lump, not attached to skin or chest wall. The histology was that of a moderately well differentiated duct carcinoma.
Histopathologic image of fibroadenoma source:John Hayman , from Wikimedia Commons

Microscopic Pathology

Histopathologic image of Phyllodes tumor Source:Nephron, from Wikimedia Commons
  • Sclerosing adenosis microscopic pathology has increased numbers of small breast acini with collapsed lumens, fibrosis surrounds the acini, considered as benign lesion with increased risk of breast cancer.
Histopathologic image of sclerosing adenosis source:Nephron, from Wikimedia Commons
Histopathologic image of atypical ductal hyperplasia source:Nephron, from Wikimedia Commons

References

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