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Surgical Pathology Criteria
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Oncocytic Carcinoma of the Breast

Definition

  • Breast carcinoma with abundant eosinophilic cytoplasm due to large numbers of mitochondria

Alternate / Historical Names

  • Malignant oncocytoma
  • Mammary epithelial oncocytoma

Diagnostic Criteria

  • Only four cases reported
    • Unrecognized cases may have been called apocrine carcinoma
  • Indistinguishable from apocrine carcinoma on H&E stain
    • Abundant granular cytoplasm
    • Sharp cell borders
    • Large round nuclei with prominent nucleoli
  • Immunohistologically differs from apocrine carcinoma
    • GCDFP15 negative
    • Antimitochondrial antibody positive
  • May be in situ or invasive

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

Original posting:: May 15, 2006

Supplemental studies

Immunohistology

  • Anti-mitochondrial antibody positive
  • GCDFP15 negative
  • Chromogranin and synaptophysin negative
  • Keratin positive 3/3 cases
  • EMA positive 2/3 cases
  • Smooth muscle actin negative
    • Peripheral myoepithelial cells positive in in situ cases

  • 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
  • CK7 and CK20 have not been tested on a series of oncocytic carcinomas, thus their utility is unknown

Prognostic/Therapeutic Markers

  • ER and PR positive in 2/3 reported cases of oncocytic carcinoma
  • 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 case

Genetic analysis

  • Her2neu status can be determined by either immunohistology or by FISH
    • The other technique can be used for borderline cases

Ultrastructure

  • Mitochondria occupying at least 60% of cytoplasm
    • Diffusely distributed throughout cytoplasm

Differential Diagnosis

Apocrine Carcinoma Oncocytic Carcinoma
GCDFP15 strong diffuse positive GCDFP15 negative
Anti-mitochondrial stain weak, focal Anti-mitochondrial antibody stain strong, diffuse
Indistinguishable on H&E stain; clinical significance of difference unknown

Clinical

  • Only 4 cases reported
    • 2 male, 2 female
    • 3 invasive, 1 in situ
  • Ages 70-77
  • No axillary or distant metastases reported
    • Too few cases reported to establish prognosis

Grading / Staging / Report

Grading

  • 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

  • Damiani S, Dina R, Eusebi V. Eosinophilic and granular cell tumors of the breast. Semin Diagn Pathol. 1999 May;16(2):117-25.
  • Damiani S, Eusebi V, Losi L, D'Adda T, Rosai J. Oncocytic carcinoma (malignant oncocytoma) of the breast. Am J Surg Pathol. 1998 Feb;22(2):221-30.
  • Costa MJ, Silverberg SG. Oncocytic carcinoma of the male breast. Arch Pathol Lab Med. 1989 Dec;113(12):1396-9.
  • 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.
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