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Surgical Pathology Criteria
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Tubular Carcinoma of the Breast

Definition

  • A low grade breast carcinoma at least 90% of appears to be composed of well differentiated tubules

Diagnostic Criteria

  • Stellate infiltrating configuration
    • Fibrous arms radiate out
    • Frequently infiltrates fat without a fibrous reaction
  • 90% composed of small, minimally branched, oval to round duct-like structures with gaping lumens
    • Ducts frequently have pointed ends ("prows")
    • Ducts lined by a single row of cells and are widely patent
    • Apical snouts common
    • Bridging by small columns of cells is OK
    • Sheet-like stratification not seen
    • Low grade cribriform carcinoma has same behavior so may constitute more than 10%
      • Report mixtures of these two simply as the predominant type
  • Nuclear grade I in at least 90% of cells
    • Slightly enlarged cells
    • Uniform nuclei, inconspicuous nucleoli, uniform chromatin
    • Pleomorphism minimal or absent
    • Mitotic figures unusual
    • Remaining 10% must not show nuclear grade III
      • Behavior may be that of the high grade component
      • Report such tumors as mixtures of two types
  • 95% are less than 2.0 cm diameter, most are less than 1 cm
  • Basement membrane absent by PAS and laminin stains and by EM
  • Myoepithelial cells absent on immunohistochemical stains
  • (Tubular carcinoma is not really tubular)

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

    Original posting: May 1, 2006
    Updates: February 13, 2009

Tubular Carcinoma Is Not Really Tubular

  • Serial sections with 3-D reconstruction shows the actual structure is not tubular
    • No continuous and/or branching tubules
  • Pattern is better described as a necklace formed by a string of beads
    • Oval to spherical cavitated blebs with tapering ends
    • Connected by short strands of cells
  • Tubulolobular carcinoma has a similar pattern but with longer connecting strands of cells
  • These findings explain the observed pattern that always appears to be cross-sections or oblique sections of tubules, but never longitudinal sections
  • See Marchio et al. 2006 for the full story

Supplemental studies

Immunohistology

  • Demonstration of myoepithelial cells can confirm the in situ nature of a process while their absence supports invasion
    • We prefer to use both p63 and calponin on problematic cases
    • A variety of markers have been used for myoepithelial cells:
    Marker Sensitivity Specificity
    Calponin Excellent Very good
    p63 Excellent Excellent
    Smooth muscle myosin heavy chain Good Excellent
    CD10 (CALLA) Good Good
    High molecular weight cytokeratin Very good Poor
    Maspin Good Poor
    S100 Good Very poor
    Actin Good Very poor
  • E-cadherin appears to be a sensitive marker of ductal differentiation vs lobular differentiation; its utility in borderline lesions is currently uncertain
  • Estrogen receptor (ER) and progesterone receptor (PR) are important markers for directing therapy and determining prognosis
    • Current consensus is that any level of positivity should be reported as positive
  • Her2neu status can be determined by either immunohistology or by FISH
    • The other technique can be used for borderline cases

Differential Diagnosis

Tubular Carcinoma Sclerosing Adenosis
Stellate, infiltrating Circumscribed, nodular
Patent ducts, gaping lumens Many ducts have obliterated lumens
Minimal branching Frequent branching
Single layer of cells Sometimes more than one layer of cells
Cells polarized to lumen Cells smaller, streaming
Myoepithelial cell absent Myoepithelial cells present

Tubular Carcinoma Microglandular Adenosis
Stellate, infiltrating Nodular or diffuse
Round to oval ducts with pointed ends and gaping lumens Uniform small round ducts with small lumens
Frequent apical snouts No apical snouts
Empty lumens Eosinophilic secretion present in at least some lumens
Larger cells, polarized to lumen Cells smaller, flatter
Round nuclei Nuclei may be flat, parallel to base
EMA positive EMA negative
Basement membrane absent Basement membrane variable
Both have rounded non-branching ducts with a single layer of cells, lacking myoepithelial cells

Tubular Carcinoma Tubular Adenosis
Stellate, infiltrating Diffuse
Frequent apical snouts No apical snouts
Ducts with frequent pointed ends Infrequent pointed ends
Empty lumens Eosinophilic secretion present in at least some lumens
Stroma desmoplastic Stroma usually hypocellular or fat
No myoepithelial cells Myoepithelial cells

Tubular Carcinoma Radial Scar
Single layer of cells Often multiple cell layers
No myoepithelial cells Myoepithelial cells present
Frequent infiltration of fat by naked tubules No bare infiltration of fat
No epithelial hyperplasia May show epithelial hyperplasia
Both have a stellate configuration with radiating fibrous arms and fibroelastotic stroma

Tubular Carcinoma Grade I Infiltrating Ductal Carcinoma, NOS
Stellate infiltration Irregular infiltration
90% tubules May have >10% ribbons or cords
Infrequent branching Frequent budding and branching
Single layer of cells May show stratification
Uniform chromatin Slightly irregular chromatin
Nucleoli inconspicuous Nucleoli may be prominent

  • A continuum exists between tubular carcinoma and well differentiated (Grade I) infiltrating ductal carcinoma
  • It is probable that a small (under 2.0 cm) well differentiated infiltrating ductal carcinoma will have a prognosis similar to that of tubular carcinoma so the distinction may not be critical
  • Grade II and III carcinomas are excluded by definition from tubular carcinoma.
  • Tubular Carcinoma Tubulolobular Carcinoma
    90% pure tubular pattern Mixed tubular and lobular patterns
    Stellate infiltrating architecture Linear infiltrative pattern, frequently concentric
    Both are typically E-cadherin positive

    Tubular Carcinoma vs Cribriform Carcinoma

    • Low grade cribriform carcinoma and tubular carcinoma both have nearly 100% survival
    • We report mixtures of these two types simply as the predominant type
      • 90% pure architectural pattern rule does not apply

    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

    Clinical

    • Long term survival reported to be 95-100%
      • Probably close to 100% if strictly defined (90% tubular)
      • 100% survival if less than 1 cm
    • 10% of large cases reported to have lymph node metastases at time of diagnosis
      • At least some of these cases may not have met the strict definition of tubular carcinoma
      • No further spread if nodes removed
    • Grade I infiltrating ductal carcinoma has nearly the same prognosis
      • Distinction in difficult cases may not be critical
    • 10-20% of patients have another carcinoma (ipsilateral or contralateral) at time of diagnosis

    Grading / Staging / Report

    Grading

    • Tubular 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

    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.
    • Deos PH, Norris HJ. Well-differentiated (tubular) carcinoma of the breast. A clinicopathologic study of 145 pure and mixed cases. Am J Clin Pathol. 1982 Jul;78(1):1-7.
    • Lagios MD, Rose MR, Margolin FR. Tubular carcinoma of the breast: association with multicentricity, bilaterality, and family history of mammary carcinoma. Am J Clin Pathol. 1980 Jan;73(1):25-30.
    • McDivitt RW, Boyce W, Gersell D. Tubular carcinoma of the breast. Clinical and pathological observations concerning 135 cases. Am J Surg Pathol. 1982 Jul;6(5):401-11.
    • Oberman HA, Fidler WJ Jr. Tubular carcinoma of the breast. Am J Surg Pathol. 1979 Oct;3(5):387-95.
    • Peters GN, Wolff M, Haagensen CD. Tubular carcinoma of the breast. Clinical pathologic correlations based on 100 cases. Ann Surg. 1981 Feb;193(2):138-49.
    • Green I, McCormick B, Cranor M, Rosen PP. A comparative study of pure tubular and tubulolobular carcinoma of the breast. Am J Surg Pathol. 1997 Jun;21(6):653-7.
    • Page DL. Special types of invasive breast cancer, with clinical implications. Am J Surg Pathol. 2003 Jun;27(6):832-5.
    • de Moraes Schenka NG, Schenka AA, de Souza Queiroz L, de Almeida Matsura M, Alvarenga M, Vassallo J. p63 and CD10: reliable markers in discriminating benign sclerosing lesions from tubular carcinoma of the breast? Appl Immunohistochem Mol Morphol. 2006 Mar;14(1):71-7.
    • Marchiò C, Sapino A, Arisio R, Bussolati G. A new vision of tubular and tubulo-lobular carcinomas of the breast, as revealed by 3-D modelling. Histopathology. 2006 Apr;48(5):556-62.

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