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Surgical Pathology Criteria

Glycogen Rich Clear Cell Carcinoma of the Breast


  • Breast carcinoma exhibiting predominantly clear cytoplasm due to glycogen

Diagnostic Criteria

  • At least 90% of the neoplastic cells have abundant clear cytoplasm due to glycogen
    • PAS positive, diastase sensitive in most cases
      • Processing may remove glycogen
    • Minor component of eosinophilic granular cytoplasm may be present
      • May suggest apocrine differentiation
    • Scant amounts of intracellular mucin may be seen in some cases
  • Growth pattern is usually that of usual infiltrating ductal carcinoma
    • Other patterns reported include lobular, tubular and medullary
  • Intraductal clear cell component may be present

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


  • PAS positive, diastase sensitive, demonstrates presence of glycogen
    • Staining may be variable due to solubility of glycogen
  • Fat 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 glycogen rich carcinomas have been found to be ER and PR positive, but GCDFP15 has not been tested on a series of them and its utility 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 glycogen ricih 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


Glycogen Rich Clear Cell Carcinoma Secretory Carcinoma
PAS positive, diastase sensitive glycogen PASd positive mucin
Cytology may be of any grade Low grade cytology
No predilection for younger patients Most cases <30 years
Behavior is that of usual invasive carcinoma Excellent prognosis


Metastatic Renal Cell Carcinoma
  • RCC is favored by the following:
    • Circumscribed mass lacking usual infiltrative pattern of breast carcinoma
      • Some primary breast carcinomas are circumscribed
    • Hemmorhage and prominent vascular pattern
  • Presence of an in situ component indicates a primary neoplasm
  • History and imaging studies may be necessary


PEComa / Sugar Cell Tumor
  • PEComa is keratin negative and HMB45 and smooth muscle actin positive


Glycogen Rich Clear Cell Carcinoma Eccrine Acrospiroma (Clear Cell Hidradenoma)
Intraparenchymal Superficial
May have an intraductal component No intraductal component
Single cell type Two cell types
No squamous differentiation Squamous eddies may be present
May have any degree of cytologic atypia Low grade cytology


Glycogen Rich Clear Cell Carcinoma Adenomyoepithelioma
Single cell type Two cell types
No neoplastic myoepithelial cell component Neoplastic myoepithelial component present
Clear cytoplasm in all areas Clear cells confined to myoepithelial cells


  • No clear difference in behavior from usual invasive breast carcinoma

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.
  • Kuroda H, Sakamoto G, Ohnisi K, Itoyama S. Clinical and pathological features of glycogen-rich clear cell carcinoma of the breast. Breast Cancer. 2005;12(3):189-95.
  • Hayes MM, Seidman JD, Ashton MA. Glycogen-rich clear cell carcinoma of the breast. A clinicopathologic study of 21 cases. Am J Surg Pathol. 1995 Aug;19(8):904-11.
  • Toikkanen S, Joensuu H. Glycogen-rich clear-cell carcinoma of the breast: a clinicopathologic and flow cytometric study. Hum Pathol. 1991 Jan;22(1):81-3.
  • Hull MT, Warfel KA. Glycogen-rich clear cell carcinomas of the breast. A clinicopathologic and ultrastructural study. Am J Surg Pathol. 1986 Aug;10(8):553-9.
  • Fisher ER, Tavares J, Bulatao IS, Sass R, Fisher B. Glycogen-rich, clear cell breast cancer: with comments concerning other clear cell variants. Hum Pathol. 1985 Nov;16(11):1085-90.

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