Columnar Cell Change with or without Flat Epithelial Atypia



Columnar Cell Change with or without Flat Epithelial Atypia







Key Facts


Terminology



  • Columnar cell change (CCC)


  • Flat epithelial atypia (FEA)


  • Encountered with increasing frequency in breast biopsies performed for mammographic microcalcifications


Microscopic Pathology



  • CCC



    • TDLUs with variably dilated acini lined by 1 or 2 layers of columnar epithelial cells


    • Cells are uniform with ovoid to elongated nuclei oriented perpendicular to basement membrane


    • Cystic spaces contain luminal secretions, flocculent material, and frequent microcalcifications


  • FEA: Similar architectural features to CCC and columnar cell hyperplasia (CCH)



    • Epithelial cells demonstrate low-grade, monomorphic-type cytologic atypia


    • Cells show nuclear enlargement, stratification, and variable nucleoli


    • May coexist with areas that fulfill diagnostic criteria for ADH or low-grade DCIS


Diagnostic Checklist



  • FEA may show genetic changes similar to those seen in low-grade DCIS and invasive carcinomas


  • Risk of FEA progressing to invasive cancer appears to be low when present as isolated finding


  • Presence of FEA should alert pathologist to search for other frequently associated lesions



    • ADH, DCIS, lobular neoplasia, and invasive carcinoma







The terminal ductal lobular units in columnar cell change demonstrate prominent distension and cystic dilatation. The luminal spaces contain secretions with granular punctate calcifications image.






The cells in flat epithelial atypia show a loss of nuclear polarity and appear stratified here. There is monomorphous low-grade cytologic atypia with chromatin changes and punctate nucleoli image.


TERMINOLOGY


Abbreviations



  • Columnar cell change (CCC)


  • Flat epithelial atypia (FEA)


Synonyms



  • Columnar cell hyperplasia


  • Columnar alteration with prominent apical snouts and secretions


  • Atypical cystic lobules


  • Unfolding breast lobules


  • Term CCC is preferred



    • Encompasses spectrum of lesions with characteristic cytoarchitectural features


Definitions



  • CCC characterized by presence of columnar epithelial cells



    • Cells line dilated terminal ductal lobular units (TDLUs)


  • Cystic spaces frequently contain luminal secretions and flocculent material



    • Frequently associated with microcalcifications


  • Encountered with increasing frequency in breast needle core biopsies



    • Most frequently seen in biopsies performed for mammographic microcalcifications


ETIOLOGY/PATHOGENESIS


Genetic Changes



  • Molecular studies show genetic changes similar to those found in low-grade DCIS and invasive cancer



    • May represent nonobligate precursor lesion


    • Likely early lesion in low-grade breast neoplasia development


CLINICAL ISSUES


Site



  • Often a multifocal process that may be bilateral



    • Rarely will produce palpable abnormality


  • Reported association and coexistence with other more serious low-grade neoplastic processes



    • Atypical ductal hyperplasia, atypical lobular hyperplasia


    • Low-grade ductal carcinoma in situ, lobular carcinoma in situ


    • Invasive low-grade ductal carcinomas (tubular carcinoma), invasive lobular carcinoma


Presentation



  • Microcalcifications on screening mammography



    • Finding will prompt needle core biopsy


Treatment



  • Surgical approaches



    • FEA found on needle core biopsy



      • Surgical excision is recommended


      • Diagnosis is upgraded to more serious lesion in 20-30% of cases


    • CCC found on needle core biopsy (without atypia)



      • Most likely incidental finding as result of microcalcifications


      • Can be followed as long as there are no other worrisome clinical or mammographic findings


Prognosis



  • Follow-up studies suggest low risk of progression to invasive cancer


  • Need to exclude association with more serious lesion, such as low-grade DCIS or tubular carcinoma


IMAGE FINDINGS


Mammographic Findings



  • Presence of microcalcifications frequent finding



MACROSCOPIC FEATURES


General Features



  • Typically no gross findings in absence of other associated lesions


MICROSCOPIC PATHOLOGY


Histologic Features



  • CCC



    • TDLUs with variably dilated acini lined by 1 or 2 layers of columnar epithelial cells



      • Enlargement and cystic dilatation of TDLUs


      • Flat growth pattern by lining epithelial cells, may show some stratification


    • Cells are uniform with ovoid to elongated nuclei



      • Nuclei show polarity, oriented in regular fashion


      • Typically perpendicular to basement membrane


    • Evenly dispersed chromatin without conspicuous nucleoli or atypia



      • Mitotic figures rarely encountered


    • Apical cytoplasmic blebs or snouts often present at luminal surface of epithelial cells


    • Flocculent secretions typically present in lumina of involved acini


    • Luminal calcifications frequently present and may be prominent


  • Columnar cell hyperplasia (CCH)



    • Features similar to CCC


    • Epithelial lining cells show varying cellular stratification, > 2 cell layers


    • Nuclei ovoid to elongated and, for the most part, oriented perpendicular to basement membrane



      • Lack conspicuous nucleoli or atypia


    • Proliferating columnar cells form small mounds, tufts, or abortive micropapillations



      • Cellular tufts and mounds are broader at base than at tips


  • FEA



    • Similar architectural features as seen in CCC and CCH



      • Morphologic spectrum based on presence and degree of epithelial atypia


      • FEA represents columnar cell lesion with varying degrees of cytologic atypia


    • Epithelial cells demonstrate low-grade, monomorphic-type cytologic atypia


    • Typically show relatively round or ovoid enlarged nuclei


    • Increased nuclear to cytoplasmic ratio


    • Nuclei can show stratification



      • Loss of polarity


      • Loss of perpendicular orientation to basement membrane


    • Nuclear chromatin may be evenly dispersed or slightly marginated



      • Nucleoli may be present and variably prominent


    • Cytologic features similar to those seen in low-grade DCIS, lesions lack architectural changes


    • FEA may coexist with areas that fulfill diagnostic criteria for ADH or low-grade DCIS


    • Finding of FEA should prompt diligent search for such areas



      • May require careful examination of deeper levels &/or additional sections


ANCILLARY TESTS


Immunohistochemistry



  • Cells are strongly ER(+) throughout lesion


  • Luminal low molecular weight keratin 8/18 positive


  • High molecular weight keratin 5/6 negative


Array CGH



  • FEA is clonal proliferation


  • Genetic changes have been described, including losses of 16q


  • Changes similar to those seen in low-grade DCIS and invasive carcinoma



DIFFERENTIAL DIAGNOSIS


Apocrine Metaplasia



  • May show cystically dilated spaces and calcifications similar to CCC


  • Apocrine metaplasia shows low nuclear to cytoplasmic ratio, eosinophilic granular cytoplasm, and round nuclei with nucleoli


  • Flat growth pattern or micropapillary growth pattern


Atypical Ductal Hyperplasia/Low-Grade Ductal Carcinoma In Situ



  • Complex architectural patterns



    • Well-developed micropapillations


    • Rigid cellular bridges, bars, and arcades


    • “Punched-out” fenestrations


  • Complex architectural patterns should be considered either ADH or DCIS


  • FEA may coexist with ADH and DCIS


High-Grade Ductal Carcinoma In Situ, Flat or “Clinging” Pattern

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Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Columnar Cell Change with or without Flat Epithelial Atypia

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