Breast

• Cystic hypersecretory carcinoma (CHC) fundamentally is an in situ process; however, terminology can be confusing to both clinicians and pathologists because it does not outright indicate that it is in situ
• Synonymous with cystic hypersecretory carcinoma in situ (CHCIS) and cystic hypersecretory DCIS (CH DCIS)
• Although CHC will be the abbreviation used for the purposes of this section, some groups prefer the term cystic hypersecretory ductal carcinoma in situ because it reinforces that the lesion is not invasive carcinoma and should be managed like DCIS

• ICD-10
  • D05.1 - intraductal carcinoma in situ of breast
    • D05.10 - intraductal carcinoma in situ of unspecified breast
    • D05.11 - intraductal carcinoma in situ of right breast
    • D05.12 - intraductal carcinoma in situ of left breast
• ICD-11: XH9SL6 - cystic hypersecretory carcinoma, intraductal

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• Low power
  • At low power, affected lobules are distorted, cystically dilated and filled with eosinophilic, colloid-like material
    • Like other forms of DCIS, the lesion has a lobular distribution
    • Colloid-like secretion resembles thyroid colloid and can show scalloping near the cells lining the duct
    • Cracking in the secretory material has been noted to resemble Venetian blinds in that the cracks are usually parallel to each other
    • Secretion is hypocellular, consisting of a few foamy macrophages
    • Calcifications are common but comedonecrosis is uncommon
  • Because CHC often arises in a spectrum of other hypersecretory lesions, close attention to the low power microarchitecture of the cells lining the ducts is important
    • CHC often shows complex pseudostratification or micropapillary architecture, whereas the cells in CHH are often flat and form a single layer
    • Solid architecture has also been noted
• Higher power
  • Cells in CHH are hyperchromatic, disorganized and pseudostratified
  • N:C ratios are increased relative to background CHH
  • Mitotic figures are present
  • Degree of nuclear atypia in most cases ranges from intermediate to high grade and resembles the degree of atypia observed in cases of clinging DCIS (Am J Surg Pathol 2014;38:45)
• Other features
  • In some cases, CHC may show periductal chronic inflammation
  • Other types of intraductal hyperplasia may coexist with CHC, including intraductal lobular neoplasia and apocrine metaplasia
  • CHC can show microinvasive carcinoma; most cases of invasive carcinoma arising in CHC are high grade and triple negative
  • In some cases, there may be background lactational-like / pregnancy-like change as well

Contributed by Andrew P. Sciallis, M.D. and Kristen E. Muller, D.O.

• Other cystic hypersecretory lesions (CHH, atypical CHH):
  • This can be diagnostically challenging as cystic hypersecretory lesions exhibit a spectrum of atypia ranging from benign (CHH) to in situ carcinoma (CHC)
    • Micropapillary architecture, prominent pseudostratification and nuclear atypia are observed in CHC
    • If a cystic hypersecretory lesion exhibits nuclear atypia but lacks significant micropapillary architecture or is small in extent, then it is best classified as atypical CHH
• Other forms of DCIS:
  • Clinging DCIS and CHC can overlap morphologically and both can contain intraluminal contents
    • In clinging DCIS, the intraluminal contents usually represent comedonecrosis and do not appear colloid-like
  • Management of CHC and DCIS is the same and largely depends on nuclear grade, necrosis, ER status and clinical extent
• Secretory carcinoma:
  • Both secretory carcinoma and CHC feature eosinophilic secretory material and secretory carcinoma can have cystic architecture
    • Secretory carcinoma often shows a variety of other architectural arrangements, including solid and microcystic
    • Secretory carcinoma often is grossly circumscribed; however, microscopically there are infiltrative margins and loss of a lobular distribution
    • Secretory carcinoma usually is triple negative but strongly positive for S100 and most cases have a ETV6::NTRK3 translocation
• Apocrine metaplasia:
  • Ducts involved by apocrine metaplasia often are cystically dilated and may show tufting that appears micropapillary
    • Apocrine metaplastic cells possess granular eosinophilic cytoplasm
    • Ducts with apocrine metaplasia may contain some secretory material but it isn’t nearly as prominent as it is in cystic hypersecretory lesions
• Juvenile papillomatosis (JP):
  • Both CHC and JP can be mass forming and show cystically dilated ducts
    • Intraductal secretion in JP is not brightly eosinophilic or colloid-like
    • Cysts in JP contain florid usual ductal hyperplasia and other patterns of proliferative breast changes

Which of the following statements regarding cystic hypersecretory carcinoma (CHC) is true?

1. CHC often arises in a background of other cystic hypersecretory lesions
2. Clinical course of CHC is much more aggressive than other types of DCIS
3. Invasive carcinoma arising in CHC usually represents secretory carcinoma
4. Most cases of CHC are ER negative
5. Most cases of CHC arise in lactating patients

A. CHC often arises in a background of other cystic hypersecretory lesions. Answer B is incorrect because although literature concerning the clinical behavior of CHC is not robust, its behavior is not significantly different from other forms of DCIS. Answer D is incorrect because most cases of CHC are ER positive. Answer E is incorrect because most cases of CHC arise in nonlactating, often postmenopausal, patients. Answer C is incorrect because invasive carcinoma arising in CHC tends to be poorly differentiated and morphologically looks different than secretory carcinoma.

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Reference: Cystic hypersecretory carcinoma