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

Secretory Carcinoma of the Breast

Definition

  • A rare (<1%) low grade breast carcinoma composed of cells with abundant granular or clear vacuolated cytoplasm

Alternate / historical names

  • Juvenile breast carcinoma
  • Juvenile secretory carcinoma

Diagnostic Criteria

  • Abundant granular cytoplasm or clear vacuolated cytoplasm
  • Tubule formation common, may have secretion in lumens
    • Follicular pattern (thyroid-like) may be seen
  • Secretory material in cells, lumens and stroma
    • Mucicarmine, alcian blue and PAS positive, diastase resistant
    • May have extracellular secretion
  • Fibrous bands often prominent
  • Low grade nuclear cytology
    • Bland, uniform nuclei
    • Mitotic figures rare
  • Sheet-like growth with mainly circumscribed margins
    • Occasional foci of infiltration are common
  • Most common under age 30
    • Most common type of breast carcinoma in children
    • May occur at any age
  • In situ component is common

    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

Alpha lactalbumin pos

S100 pos
Lysozyme pos
Salivary type amylase pos
CEA variable
GCDFP15 (BRST2) variable

  • Demonstration of myoepithelial cells can confirm the in situ or benign 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
  • 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

Genetic Analysis

  • ETV6-NTRK3 gene fusion has been reported in 12/13 secretory carcinomas and is absent in other breast carcinomas

Differential Diagnosis

Histiocytoid Carcinoma Secretory Carcinoma
All reported cases >40 years Most cases <30 years
Scant or granular mucin Abundant cytoplasmic mucin
GCDFP15 strong positive GCDFP15 variable
Aggressive behavior Excellent prognosis

Mucinous Carcinoma Secretory Carcinoma
1/3 of volume is extracellular mucin Largely intracellular mucin
Carcinoma cells float in mucin Cells grow in sheets or tubules
No predilection for younger patients Most cases <30 years

Signet Ring Carcinoma Secretory Carcinoma
One or few vacuoles that indent nucleus Abundant granular to clear cytoplasm
May be nuclear grade I or II Low nuclear grade
Often associated with classic lobular carcinoma pattern No association with lobular carcinoma
No predilection for young patients Most cases <30 years
May show aggressive behavior Excellent prognosis
Signet ring carcinoma is usually a variant pattern of lobular carcinoma

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

Apocrine Carcinoma Secretory Carcinoma
Large vesicular nuclei with prominent nucleoli Low grade nuclei with inconspicuous nucleoli
Cytoplasm granular, eosinophilic Cytoplasm granular or clear and vacuolated
PASd may show granular cytoplasmic staining PASd shows abundant cytoplasmic mucin
No predilection for young patients Most cases <30 years
Many show aggressive behavior Excellent prognosis

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

Clinical

  • Very rare
    • Less than 1% of infiltrating carcinomas
    • Reports range from 1/3000 to 4/7038 breast carcinomas
  • Most common under age 30
    • Most common type of breast carcinoma in children and juveniles
    • May occur at any age
  • Has been reported in males, including prepubertal boys
  • Excellent prognosis even when axillary metastases are present
    • Essentially no children or juveniles die of carcinoma
      • Rare reports of pediatric cases recurring up to 20 years later, causing death
    • Rarely adults will develop distant metastases
      • Size and extent of infiltration may be the most important determinants of metastatic potential in adults.

Grading / Staging / Report

Grading

  • Secretory 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 lesions preferentially presenting in juvenile/adolescent/pubertal breast

(These may, of course occasionally present at other ages and other lesions may rarely present at this age)

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.
  • Tavassoli FA, Norris HJ. Secretory carcinoma of the breast. Cancer. 1980 May 1;45(9):2404-13.
  • Hirokawa M, Sugihara K, Sai T, Monobe Y, Kudo H, Sano N, Sano T. Secretory carcinoma of the breast: a tumour analogous to salivary gland acinic cell carcinoma? Histopathology. 2002 Mar;40(3):223-9.
  • Krausz T, Jenkins D, Grontoft O, Pollock DJ, Azzopardi JG. Secretory carcinoma of the breast in adults: emphasis on late recurrence and metastasis. Histopathology. 1989 Jan;14(1):25-36.
  • Lamovec J, Bracko M. Secretory carcinoma of the breast: light microscopical, immunohistochemical and flow cytometric study. Mod Pathol. 1994 May;7(4):475-9.
  • de Bree E, Askoxylakis J, Giannikaki E, Chroniaris N, Sanidas E, Tsiftsis DD. Secretory carcinoma of the male breast. Ann Surg Oncol. 2002 Aug;9(7):663-7.
  • Tognon C, Knezevich SR, Huntsman D, Roskelley CD, Melnyk N, Mathers JA, Becker L, Carneiro F, MacPherson N, Horsman D, Poremba C, Sorensen PH. Expression of the ETV6-NTRK3 gene fusion as a primary event in human secretory breast carcinoma. Cancer Cell. 2002 Nov;2(5):367-76.
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