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Surgical Pathology Criteria
http://surgpathcriteria.stanford.edu/

Low Grade Adenosquamous Carcinoma of the Breast

Definition

  • Low grade breast carcinoma exhibiting both glandular and squamous differentiation characterized by infiltrating, frequently compressed lumens

Alternate / Historical Names

  • Metaplastic carcinoma
  • Syringomatous squamous tumor

Diagnostic Criteria

  • Infiltrating round to irregular tubules, often compressed and comma shaped
    • Resembles syringoma
    • Lumens may contain amorphous, eosinophilic material or keratin
  • Myoepithelial cells prominently present around tubules
    • Results in at least a double cell layer
  • Squamous differentiation variable (5-80% of tubules)
    • Overt keratinization less common than intercellular bridges
  • Abundant collagenous stroma
    • 2 of 32 cases reported with osteocartilaginous metaplasia of stroma
    • Occasional lymphoid nodules present
  • Bland cytology
    • Mitotic figures rare
    • No necrosis
  • May be associated with other lesions
    • 12/32 cases associated with intraductal papillary lesions
    • 3/32 cases associated with adenomyoepithelioma
    • 3/32 cases associated with collagenous spherulosis
  • May be considered a low grade variant of metaplastic carcinoma or an adenomyomatous lesion
  • It has been proposed that this is the same lesion as infiltrating syringomatous adenoma of the nipple differing only in location
    • Adenosquamous carcinoma rarely may metastasize but this has not been reported for syringomatous adenoma

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

Original posting / updates: 5/1/06, 12/25/12

Supplemental studies

Immunohistology

  • All cases reported to be ER and PR negative
  • GCDFP15 negative
  • Myoepithelial layer present around tubules
    • Smooth muscle actin, p63, calponin, CD10, smooth muscle myosin
    • Extent of staining is highly variable (Kawaguchi 2012)

Differential Diagnosis

  • Metaplastic carcinoma NOS
    • Adenosquamous carcinoma may be considered a variant of metaplastic carcinoma
      • It should be diagnosed separately because of its distinct histologic appearance and its low grade behavior
    • Metaplastic carcinoma includes pure squamous carcinoma and usual infiltrating carcinoma with squamous metaplasia plus those with mesenchymal metaplasia

 

    Tubular Carcinoma Low Grade Adenosquamous Carcinoma
    Uniform, gaping tubules Irregular, frequently compressed lumens
    Tubules frequently have pointed ends Tubules frequently have long comma-shaped tails
    No squamous differentiation At least focal squamous differentiation
    No myoepithelial component Myoepithelial cells prominently present around tubules
    Both are low grade cytologically and clinically

    .

    Infiltrating Syringomatous Adenoma of the Nipple Low Grade Adenosquamous Carcinoma
    Involves dermis and subcutis Parenchymal lesion
    No metastases reported Infrequent metastases reported
  • Some consider these to be the same entity in different locations
  • Histologic appearance is identical
  • Small numbers of cases and differences due to superficiality could account for the difference in behavior reported
  •  

    Low Grade Adenosquamous Carcinoma Adenomyoepithelioma
    Squamous differentiation frequent Squamous differentiation not described
    Infiltrative pattern Circumscribed, not infiltrative
    Otherwise the lesions may be identical

     

Clinical

  • Same age range as usual infiltrative carcinoma (33-88 years)
  • Low grade, but malignant, behavior
    • 1/12 with axillary dissection had a single positive node
    • Of 25 patients with at least one year followup
      • 5 with local recurrence
        • One progressed to death
    • All metastases to nodes or distant sites in patients <40 years of age and >3 cm diameter primary

Grading / Staging / Report

Grading

  • Adenosquamous carcinoma is by definition low grade

  • 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.
  • Rosen PP, Ernsberger D. Low-grade adenosquamous carcinoma. A variant of metaplastic mammary carcinoma. Am J Surg Pathol. 1987 May;11(5):351-8.
  • Drudis T, Arroyo C, Van Hoeven K, Cordon-Cardo C, Rosen PP. The pathology of low-grade adenosquamous carcinoma of the breast. An immunohistochemical study. Pathol Annu. 1994;29 ( Pt 2):181-97.
  • Van Hoeven KH, Drudis T, Cranor ML, Erlandson RA, Rosen PP. Low-grade adenosquamous carcinoma of the breast. A clinocopathologic study of 32 cases with ultrastructural analysis. Am J Surg Pathol. 1993 Mar;17(3):248-58.
  • Suster S, Moran CA, Hurt MA. Syringomatous squamous tumors of the breast. Cancer. 1991 May 1;67(9):2350-5.
  • Foschini MP, Pizzicannella G, Peterse JL, Eusebi V. Adenomyoepithelioma of the breast associated with low-grade adenosquamous and sarcomatoid carcinomas. Virchows Arch. 1995;427(3):243-50.
  • Ferrara G, Nappi O, Wick MR. Fine-needle aspiration cytology and immunohistology of low-grade adenosquamous carcinoma of the breast. Diagn Cytopathol. 1999 Jan;20(1):13-8.
  • Kawaguchi K, Shin SJ. Immunohistochemical staining characteristics of low-grade adenosquamous carcinoma of the breast. Am J Surg Pathol. 2012 Jul;36(7):1009-20

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