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atypical lobular hyperplasia

Friday 20 November 2015

ALH; lobular intraepithelial neoplasia 1 (LIN1)

PO

Definition :

ALH is a part of the spectrum of lobular neoplasia, which also includes LCIS.

Images

- Atypical lobular hyperplasia (or LCIS) growing in a pagetoid distribution

- Atypical Lobular Hyperplasia (ALH) at breastpathology.info

Clinical

- Usually not associated with specific mammographic findings.
- ALH is frequently associated with columnar cell lesions and flat epithelial atypia.

- ALH does not form a palpable mass.
- ALH is an ncidental finding on core biopsy with no reliable radiological features.
- Usually an incidental finding at biopsy, not a palpable mass.
- ALH is less commonly associated with low grade invasive carcinomas which may have mammographically-detectable calcifications, density or mass targeted on biopsy (Am J Surg Pathol 1998;22:1521, Am J Surg Pathol 2007;31:417)

Microscopy

- Criteria of Page et al: (Schnitt and Collins: Biopsy Interpretation of the Breast, 2nd Edition)

  • Distends 50% or more acini within a lobule (so resembles LCIS), but not uniformly present throughout entire lobule OR
  • Involves all acini in a TDLU (so resembles LCIS) but does not distend the acini (i.e. caliber of the involved acini is similar to that of uninvolved acini)

- The acinar lumen are not completely obliterated.

- monotonous cell population

  • The cells are not as monotonous and are less regularly spaced than those seen in lobular neoplasia.
  • The cell population can appear somewhat monotonous, not all the lumen are completely obliterated.

- The cells appear more pleomorphic and cohesive than those seen in lobular neoplasia LIN2.
- The acini are less distended than that seen in lobular neoplasia, and the lumen are not completely filled by cells.
- The cells are not regularly spaced, and the cells have a somewhat variable appearance.

- Ductal involvement by cells of atypical lobular hyperplasia

  • Cells of atypical lobular hyperplasia can involve a terminal duct lobular unit (TDLU)
  • Can involve ducts: alteration occurs around the duct as outpouchings producing a clover-leaf pattern
  • When malignant cells spread in a nodular fashion, a clover-leaf pattern is produced.
  • possibly displaying pagetoid involvement of a terminal duct
  • The cells spread between the luminal epithelium and underlying myoepithelial layer.

- Cells of atypical lobular hyperplasia can also involve sclerosing adenosis

  • There is an increase in glandular elements as well as stromal proliferation.
  • If viewed at low power, the overall lobular architecture would be retained.

- May be no/minimal inflammatory response

  • no surrounding inflammatory response.
  • The inflammatory response is usually minimal or absent in atypical lobular hyperplasia and LCIS as compared to ductal carcinoma in situ (DCIS).

- ALH can also be observed in a fibroadenoma, in slerozing adenosis, an atrophic unit, a papilloma or micropapilloma.

- Lacks intracytoplasmic mucin

Immunochemistry

- E-cadherin-

  • The E-cadherin stain is focally negative in cells of atypical lobular hyperplasia.

- ER+ (ER alpha stronger than ER beta, Virchows Arch 2007;451:893)
- CK34betaE12+ (polarized)
- p120catenin+ (cytoplasmic, not membranous staining, Am J Surg Pathol 2007;31:427)
- PR+

- alpha-catenin- and beta-catenin-

Cytology

- Loosely cohesive cell clusters composed of uniform cells with occasional intracytoplasmic lumina, minimal nuclear atypia but frequent eccentric nuclei.

Differential diagnosis

- Solid ductal intraepithelial neoplasias (DCINs)

  • usually cohesive cells with multiple secondary lumina,
  • rosette-like nuclei,
  • E-cadherin+

Cytogenetics

-  diploid

Prognosis

- 19% develop invasive cancer at mean 15 years after diagnosis (4-5x usual risk),
- 42% are special subtypes with good prognosis (Cancer 2006;107:1227)
- 4-5x usual risk of carcinoma, higher in ipsilateral breast, higher if age @<@ 50 years (Am J Surg Pathol 2002;26:421, Cancer 2007;109:180);
- risk increased further if ductal involvement (Hum Path 1988;19:201)

Management

If present at core biopsy, is surgical excision appropriate?

- Many studies support excision due to risk of subsequent in situ carcinoma or invasive carcinoma.
- Yes because:

  • ductal carcinoma in situ (DCIS)/invasive carcinoma occurs in 6-8% (Archives 2008;132:979, Am J Surg Pathol 2007;31:717),
  • invasive ductal/lobular carcinoma occurs in 25% (Am J Surg Pathol 2005;29:534, AJR Am J Roentgenol 2008;190:637)

- No, because there is no significantly increased risk and any subsequent cancer is diffuse, bilateral and not at location of biopsy (Am J Surg 2009;198:792)

- No, unless:

  • radiologic-pathologic discordance suggests that the targeted lesion was not excised,
  • other high risk lesions such as atypical ductal hyperplasia (ADH) are present that would warrant further surgery,
  • ALH has features resembling DCIS (Am J Surg Pathol 2002;26:1095),
  • ALH has pleomorphic features (Mod Pathol 2008;21:1208, Cancer 2008;112:2152),
  • if diffuse lobular neoplasia at core biopsy (Breast J 2007;13:55)

- Lifelong follow up is recommended.

Images

- http://www.hsc.stonybrook.edu/breast-atlas/I-22.htm

See also

- mammary lobular neoplasias
- mammary precursor lesions

PO

Microscopy

- Criteria of Page et al: (Schnitt and Collins: Biopsy Interpretation of the Breast, 2nd Edition)

  • Distends 50% or more acini within a lobule (so resembles LCIS), but not uniformly present throughout entire lobule OR
  • Involves all acini in a TDLU (so resembles LCIS) but does not distend the acini (i.e. caliber of the involved acini is similar to that of uninvolved acini)
    - May be no/minimal inflammatory response
    - Can involve ducts: alteration occurs around the duct as outpouchings producing a clover-leaf pattern)
    - Lacks intracytoplasmic mucin
    - Atypical cells with focal preservation of luminal spaces
    - Can involve sclerosing adenosis
    - pagetoid ductal involvement and clover leaf pattern
    - The distended lobules are occupied by atypical lobular cells with round to oval nuclei and small nucleoli. Rare myoepithelial cells with small dark nuclei remain.

Associations

- Frequently associated with columnar cell lesions and flat epithelial atypia; less commonly associated with low grade invasive carcinomas which may have mammographically-detectable calcifications, density or mass targeted on biopsy (Am J Surg Pathol 1998;22:1521, Am J Surg Pathol 2007;31:417)

Clinical synopsis

- Usually not associated with specific mammographic findings.
- Does not form a palpable mass.
- Incidental finding on core biopsy with no reliable radiological features.
- Usually an incidental finding, not a palpable mass.

Prognosis

- 19% develop invasive cancer at mean 15 years after diagnosis (4-5x usual risk),
- 42% are special subtypes with good prognosis (Cancer 2006;107:1227)
- Lifelong follow up is recommended.
- 4-5x usual risk of carcinoma

  • higher in ipsilateral breast
  • higher if age @<@ 50 years (Am J Surg Pathol 2002;26:421, Cancer 2007;109:180);
  • risk increased further if ductal involvement (Hum Path 1988;19:201)

- If present at core biopsy, is surgical excision appropriate? (PO)

  • Many studies support excision due to risk of subsequent in situ or invasive carcinoma
  • Yes
    • DCIS/invasive carcinoma occurs in 6-8% (Archives 2008;132:979, Am J Surg Pathol 2007;31:717),
    • invasive ductal/lobular carcinoma occurs in 25% (Am J Surg Pathol 2005;29:534, AJR Am J Roentgenol 2008;190:637)
  • No, unless:
    • radiologic-pathologic discordance suggests that the targeted lesion was not excised,
    • other high risk lesions such as ADH are present that would warrant further surgery,
    • ALH has features resembling DCIS (Am J Surg Pathol 2002;26:1095),
    • ALH has pleomorphic features (Mod Pathol 2008;21:1208, Cancer 2008;112:2152),
    • or there is diffuse lobular neoplasia at core biopsy (Breast J 2007;13:55)
  • No: because there is no significantly increased risk and any subsequent cancer is diffuse, bilateral and not at location of biopsy (Am J Surg 2009;198:792)

CGH (16897748)

- gains

  • 2p11.2 gain

- losses

  • 7p11-p11.1 loss
  • 22q11.1 loss
  • 16q21-q23.1 loss

References

- Mastracci TL, Shadeo A, Colby SM, Tuck AB, O’Malley FP, Bull SB, Lam WL, Andrulis IL. Genomic alterations in lobular neoplasia: a microarray comparative genomic hybridization signature for early neoplastic proliferationin the breast. Genes Chromosomes Cancer. 2006 Nov;45(11):1007-17. PMID: 16897748