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Surgical Pathology Criteria

Lipid Rich Carcinoma of the Breast


  • Breast carcinoma exhibiting clear cytoplasm due to lipid

Alternate / Historical Names

  • Lipid secreting carcinoma

Diagnostic Criteria

  • Clear, multivacuolated or foamy cytoplasm
    • May have areas of oxyphilic cytoplasm
  • Abundant intracytoplasmic lipid
    • Oil red O or Sudan III stain positive
      • Requires unprocessed tissue
  • May have any grade cytology
  • Wide variety of patterns
    • Nests, cords, sheets, alveoli

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

Supplemental studies

Immunohistology and Other Stains

  • Oil Red O and Sudan III fat stains positive
    • Requires unprocessed tissue
  • Actin and S100 negative
  • PAS stain negative

  • 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
  • At least some lipid rich carcinomas have been found to be ER and PR positive
  • GCDFP15 has been described as variable or weak but it has not been tested on a series of lipid rich carcinomas and its sensitivity is unknown

  • Immunologic markers useful for identification of breast carcinoma
  • GCDFP15 (BRST2) Estrogen Receptor Progesterone Receptor PAX8
    Infiltrating ductal carcinoma 60-70% 75% 50-60% 0%
    Infiltrating lobular carcinoma 60-70% >95% 80% 0%
    Lung adenocarcinoma 0-1% <5% <5% 0%
    Ovarian adenocarcinoma 1-5% 50-100% 40-90% 90-100%
    Endometrioid adenocarcinoma negative 70% 70%  
    GI adenocarcinoma negative <5% 1-10% 0%
    Pancreatic adenocarcinoma negative negative 0-5% 0%
    Cholangiocarcinoma negative negative 30%  
    Thyroid carcinoma negative 20% 30% 100%
  • Sweat gland and salivary gland neoplasms may also be positive for GCDFP15, ER and PR
  • Prostatic adenocarcinoma may be positive for GCDFP15

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

    CK7 and CK20 expression in carcinomas

    CK7+20+ CK7-20+
    Ovary mucinous 90% Colorectal adeno 80%
    Transitional cell 65% Merkel cell 70%
    Pancreas adeno 65% Gastric adeno 35%
    Cholangio 65%  
    Gastric adeno 40%  
    Excluded tumors 5% or less Carcinoid; Germ cell; Esoph squam; Head/neck squam; Hepato-cellular; Lung small cell & squam; Ovary non-mucinous; Renal adeno Excluded tumors 5% or less Breast; Carcinoid lung; Cholangio; Esoph squam; Germ cell; Lung all types; Hepato-cellular; Ovary; Pancreas adeno; Renal adeno; Transitional cell; Uterus endometrioid
    CK7+20- CK7-20-
    Ovary non-mucinous 100% Adrenal 100%
    Thyroid (all 3 types) 100% Seminoma & Yolk Sac 95%
    Breast 90% Prostate 85%
    Lung adeno 90% Hepatocellular 80%
    Uterus endometrioid 85% Renal adeno 80%
    Embryonal 80% Carcinoid intestinal & lung 80%
    Mesothelioma 65% Lung small cell & squam 75%
    Transitional cell 35% Esoph squam 70%
    Pancreas adeno 30% Head/neck squam 70%
    Cholangio 30% Mesothelioma 35%
    Excluded tumors 5% or less Colorectal adeno; Ovary mucinous; Yolk Sac; Seminoma Excluded tumors 5% or less Breast; Cholangio; Lung adeno; Ovary; Pancreas adeno
  • Derived from Chu PG, Weiss LM. Histopathology 2002, 40:403-439 and other sources

Prognostic/Therapeutic Markers

  • 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

Differential Diagnosis


Glycogen Rich Clear Cell Carcinoma Lipid Rich Carcinoma
PAS positive, diastase sensitive glycogen PAS negative
Lipid stain negative Lipid stain positive
Clear cytoplasm Cytoplasm clear to multivacuolated


Lipid Rich Carcinoma Secretory Carcinoma
Scant PASd positivity in cells Abundant PASd positive mucin
Fat stains positive Fat stains negative
May have any grade cytology Low grade cytology
No predilection for young patients Most cases <30 years
Many show aggressive behavior Excellent prognosis


Lipid Rich Carcinoma Apocrine Carcinoma
Cytoplasm clear to multivacuolated Cytoplasm nearly uniformly granular
Cytoplasm at most focally eosinophilic Cytoplasm nearly uniformly eosinophilic
Scant PASd positivity in cells Frequently PASd positive
Fat stains positive Fat stains negative
GCDFP15 variable/weak GCDFP15 strong positive


Lipid Rich Carcinoma Histiocytoid Carcinoma
Lipid stain positive Lipid stain negative
GCDFP15 variable to weak GCDFP15 strong positive
Mucin negative Mucin positive intracytoplasmic lumens or granular cytoplasm
May have any grade cytology Low grade cytology
Lacks intracytoplasmic lumens May have intracytoplasmic lumens


  • Few cases reported but many have shown an aggressive course
  • One case reported in male and one in a child

Grading / Staging / Report


  • 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)


  • 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


  • 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


Infiltrating Breast Carcinomas


  • Rosen PP, Oberman HA . Tumors of the Mammary Gland, Atlas of Tumor Pathology, AFIP Third Series, Fascicle 7, 1993
  • 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.
  • Wrba F, Ellinger A, Reiner G, Spona J, Holzner JH. Ultrastructural and immunohistochemical characteristics of lipid-rich carcinoma of the breast. Virchows Arch A Pathol Anat Histopathol. 1988;413(5):381-5.
  • Ramos CV, Taylor HB. Lipid-rich carcinoma of the breast. A clinicopathologic analysis of 13 examples. Cancer. 1974 Mar;33(3):812-9.
  • van Bogaert LJ, Maldague P. Histologic variants of lipid-secreting carcinoma of the breast. Virchows Arch A Pathol Anat Histol. 1977 Oct 7;375(4):345-53.
  • Aboumrad MH, Horn RC Jr, Fine G. Lipid-secreting mammary carcinoma. Report of a case associated with Paget's disease of the nipple. Cancer. 1963 Apr;16:521-5.
  • Reis-Filho JS, Fulford LG, Lakhani SR, Schmitt FC. Pathologic quiz case: a 62-year-old woman with a 4.5-cm nodule in the right breast. Lipid-rich breast carcinoma. Arch Pathol Lab Med. 2003 Sep;127(9):e396-8.
  • Mazzella FM, Sieber SC, Braza F. Ductal carcinoma of male breast with prominent lipid-rich component. Pathology. 1995 Jul;27(3):280-3.
  • Balik E, Taneli C, Cetinkursun S, Yazici M, Cetingul N, Erhan Y, Haydaroglu A, Oztop S. Lipid secreting breast carcinoma in childhood: a case report. Eur J Pediatr Surg. 1993 Feb;3(1):48-9.
  • Vera-Sempere F, Llombart-Bosch A. Lipid-rich versus lipid-secreting carcinoma of the mammary gland. Pathol Res Pract. 1985 Nov;180(5):553-8.
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