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  • Surgical Pathology Criteria
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    Adenoid Cystic Carcinoma of the Breast

    Definition

    • Very rare type of breast carcinoma resembling adenoid cystic carcinoma of other sites

    Diagnostic Criteria

    • Biphasic cell population
      • One population with phenotype of duct lining cells
        • Surrounds small lumens
        • CK5/6, CK7, CK8/18, ckit positive
        • Small cells with sparse cytoplasm and indistinct nucleoli
      • One population with phenotype of myoepithelial cells
        • Surrounds many nests and basement membrane cores
        • p63, actin positive
    • Various growth patterns, usually at least focally cribriform
      • Biphasic, cylindromatous
        • Cribriform growth surrounding cores of basement membrane material
          • PASd positive
          • Continuous with surrounding basement membrane
        • Indistinct true lumens, frequently discernable only on immunohistologic stains
      • Trabecular
      • Tubular
      • Solid (predominantly myoepithelial cells)
      • Basaloid (predominantly lumenal cells)
    • Rarely exhibits sebaceous or squamous differentiation
    • Frequently grossly circumscribed but microscopically invasive
    • May be multifocal

    Richard L Kempson MD
    Robert V Rouse MD
    Department of Pathology
    Stanford University School of Medicine
    Stanford CA 94305-5342

    Original posting:: December 23, 2006

    Supplemental studies

    Immunohistology

    • Biphasic cell population
      Lumenal Cells Myoepithelial Cells
    p63 negative positive
    Actin negative positive
    Calponin negative negative
    Smooth muscle myosin negative negative
    ckit positive variable, see below
    CK5/6, CK7, CK8/18 positive negative
    • Laminin and Collagen type IV surround basement membrane cores
    • Estrogen and Progesterone Receptors negative in most studies
      • Some reports of positivity:
        • 3/20 in study of Mastropasqua 2005, but none over 5%
        • 5/19 in study of Kleer 1998, but series included higher grade tumors
    • Her2neu negative
    • Reports of ckit (CD117) expression in myoepithelial component are conflicting
      • Mastropasqua reports them to be negative
      • Azoulay and Crisi report them to be negative in cribriform pattern but positive in diffuse pattern
        • Published figures of Azoulay look positive in both patterns
      • Rabban reports positivity only in lumenal (ductal) cells

    Differential Diagnosis

    Adenoid Cystic Carcinoma Cribriform Carcinoma
    Cores of PASd positive basement membrane No basment membrane cores
    Myoepithelial component present No myoepithelial component
    ckit positive population No ckit positivity
    Estrogen receptor generally negative Estrogen receptor uniformly positive
    No DCIS DCIS may be present
    Low grade cribriform carcinoma and adenoid cystic carcinoma both have nearly 100% survival
    Adenoid Cystic Carcinoma Collagenous Spherulosis
    Grossly visible or palpable lesion Nearly always an incidental microscopic finding
    Invasive architecture Circumscribed, intraductal or intralobular
    Uniform cores of basement membrane material Variable, frequently fibrillar spherules
    Nuclei slightly enlarged compared to normal Nuclei identical in size and appearance to normal
    CD117 positive lumenal cells CD117 negative
    Calponin, smooth muscle myosin negative (even myoepithelial component) Calponin, smooth muscle myosin positive
    Both contain myoepithelial and epithelial components

    Clinical

    • Long term survival virtually 100%
      • Apparently even with axillary metastases
    • Very rare axillary metastases
      • May be related to grade
    • Extremely rare distant metastases
      • May be related to grade
    • May recur if incompletely excised
      • May give rise to extensive disease within the breast
    • Very rare (0.1-1% of breast carcinomas)

    Grading / Staging / Report

    Grading

    • Grading based on salivary gland criteria has been proposed:
      • Architectural
        • Grade I: no solid areas
        • Grade II: <30% solid areas
        • Grade III: at least 30% solid areas
      • Nuclear
        • Grade 1: mild atypia, slight pleomorphism, 0-1 mitotic figures/10 hpf
        • Grade 2: moderate atypia, 2-4 mitotic figures/10 hpf
        • Grade 3: higher degree of atypia, prominent nucleoli, 5-10 mitotic figures/10 hpf
      • Increased architectural and nuclear grade have been reported to be associated with increased axillary metastases but not with decreased survival (Kleer 1998; Mastropasqua 2005)
    • Until the value of various grading methods is resolved, standard grading should also be reported:

    • Bloom-Scarff-Richardson grading scheme is most widely used
    • Total score and each of the three components should be reported
    • Based on invasive area only
    Tubule formation Score
    >75% tubules 1
    10-75% tubules 2
    <10% tubules 3

     

    Nuclear pleomorphism (most anaplastic area) Score
    Small, regular, uniform nuclei, uniform chromatin 1
    Moderate varibility in size and shape, vesicular, with visible nucleoli 2
    Marked variation, vesicular, often with multiple nucleoli 3

     

    Mitotic figure count per 10 40x fields (depends on area of field, see key below) Score
    0.096 mm2 0.12 mm2 0.16 mm2 0.27 mm2 0.31 mm2
    0-3 0-4 0-5 0-9 0-11 1
    4-7 5-8 6-10 10-19 12-22 2
    >7 >8 >10 >19 >22 3
    • Olympus BX50, BX40 or BH2 or AO or Nikon with 15x eyepiece: 0.096 mm2
    • AO with 10x eyepiece: 0.12 mm2
    • Nikon or Olympus with 10x eyepiece: 0.16 mm2
    • Leitz Ortholux: 0.27 mm2
    • Leitz Diaplan: 0.31 mm2
    • Mitotic count figures based on original data presented for Leitz Ortholux by Elston and Ellis 1991, with modifications based on pubished and measured areas of view
    • Evaluate regions of most active growth, usually in cellular areas at periphery
    • We employ strict criteria for identification of mitotic figures
    Sum of above three components Overall grade
    3-5 points Grade I (well differentiated)
    6-7 points Grade II (moderately differentiated)
    8-9 points Grade III (poorly differentiated)

    Staging

    • TNM staging is the most widely used scheme for breast carcinomas but is not universally employed
    • Critical staging criteria for regional lymph nodes
      • Isolated tumor cell clusters
        • Usually identified by immunohistochemistry
          • Term also applies if cells identified by close examination of H&E stain
        • No cluster may be greater than 0.2 mm
        • Multiple such clusters may be present in the same or other nodes
      • Micrometastasis
          • Greater than 0.2 mm, none greater than 2.0 mm
      • Metastasis
        • At least one carcinoma focus over 2.0 mm
          • If one node qualifies as >2.0 mm, count all other nodes even with smaller foci as involved
        • Critical numbers of involved nodes: 1-3, 4-9 and 10 and over
      • Note extranodal extension

    Report

    • Excisions: the following are important elements that must be addressed in the report for infiltrative breast carcinomas
      • Grade
        • Total score and individual components
      • Size of neoplasm
        • Give 3 dimensions or greatest dimension
        • Critical cutoffs occur at 0.5 cm and at 2 cm
      • Margins of resection
        • Measure and report the actual distance of both invasive and in situ carcinoma
      • Angiolymphatic invasion
        • Indicate if confined to tumor mass, outside tumor mass or in dermis
      • (Extensive DCIS is not currently felt to be a significant predictor of behavior)
      • Results of special studies performed for diagnosis
      • Results of prognostic special studies performed
        • ER, PR, Proliferation marker, Her2neu
        • If studies were performed on a prior specimen, refer to that report and give results
    • Needle or core biopsies
      • Provisional grade may be given but may defer to excision for definitive grade
      • Presence of absence of angiolymphatic invasion
      • Results of special studies performed for diagnosis
      • Results of prognostic special studies if performed
        • ER, PR, Proliferation marker, Her2neu
        • State if studies are deferred for a later excision specimen
    • Regional lymph nodes
      • Report findings as described above

    Lists

    Infiltrating Breast Carcinomas

    Breast Tumors and Lesions Exhibiting Reactivity for Muscle/Myoepithelial Markers

    (Most benign lesions with an epithelial component will have a myoepithelial cell layer)

    Bibliography

    • Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology. 1991 Nov;19(5):403-10.
    • Mastropasqua MG, Maiorano E, Pruneri G, Orvieto E, Mazzarol G, Vento AR,
      Viale G. Immunoreactivity for c-kit and p63 as an adjunct in the diagnosis of adenoid cystic carcinoma of the breast. Mod Pathol. 2005 Oct;18(10):1277-82.
    • Azoulay S, Lae M, Freneaux P, Merle S, Al Ghuzlan A, Chnecker C, Rosty C, Klijanienko J, Sigal-Zafrani B, Salmon R, Fourquet A, Sastre-Garau X, Vincent-Salomon A. KIT is highly expressed in adenoid cystic carcinoma of the breast, a basal-like carcinoma associated with a favorable outcome. Mod Pathol. 2005 Dec;18(12):1623-31.
    • Crisi GM, Marconi SA, Makari-Judson G, Goulart RA. Expression of c-kit in adenoid cystic carcinoma of the breast. Am J Clin Pathol. 2005 Nov;124(5):733-9.
    • Page DL. Adenoid cystic carcinoma of breast, a special histopathologic type with excellent prognosis. Breast Cancer Res Treat. 2005 Oct;93(3):189-90.
    • Page DL. Special types of invasive breast cancer, with clinical implications. Am J Surg Pathol. 2003 Jun;27(6):832-5.
    • Peters GN, Wolff M. Adenoid cystic carcinoma of the breast. Report of 11 new cases: review of the literature and discussion of biological behavior. Cancer. 1983 Aug 15;52(4):680-6.
    • Ro JY, Silva EG, Gallager HS. Adenoid cystic carcinoma of the breast. Hum Pathol. 1987 Dec;18(12):1276-81.
    • Tavassoli FA, Norris HJ. Mammary adenoid cystic carcinoma with sebaceous differentiation. A morphologic study of the cell types. Arch Pathol Lab Med. 1986 Nov;110(11):1045-53.
    • Wells CA, Nicoll S, Ferguson DJ. Adenoid cystic carcinoma of the breast: a case with axillary lymph node metastasis. Histopathology. 1986 Apr;10(4):415-24.
    • Zaloudek C, Oertel YC, Orenstein JM. Adenoid cystic carcinoma of the breast. Am J Clin Pathol. 1984 Mar;81(3):297-307.
    • Kleer CG, Oberman HA. Adenoid cystic carcinoma of the breast: value of histologic grading and proliferative activity. Am J Surg Pathol. 1998 May;22(5):569-75.
    • Shin SJ, Rosen PP. Solid variant of mammary adenoid cystic carcinoma with basaloid features: a study of nine cases. Am J Surg Pathol. 2002 Apr;26(4):413-20.
    • Trendell-Smith NJ, Peston D, Shousha S. Adenoid cystic carcinoma of the breast: a tumour commonly devoid of oestrogen receptors and related proteins. Histopathology. 1999 Sep;35(3):241-8.
    • Rabban JT, Swain RS, Zaloudek CJ, Chase DR, Chen YY. Immunophenotypic overlap between adenoid cystic carcinoma and collagenou spherulosis of the breast: potential diagnostic pitfalls using myoepithelial markers. Mod Pathol. 2006 Oct;19(10):1351-7.
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    © 2005  Stanford University School of Medicine