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Surgical Pathology Criteria
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Medullary Carcinoma of the Breast

Definition

  • A rare breast carcinoma with a syncitial growth pattern and high grade cytology reported to have a good prognosis

Diagnostic Criteria

  • Syncitial growth pattern in at least 75% of tumor
    • Cell margins not distinct
  • Heavy mononuclear inflammatory infiltrate
  • Microscopically circumscribed
    • No infiltration
  • Absence of neoplastic ducts or glands
  • High grade pleomorphic nuclei with prominent nucleoli
  • We require all five features to make the diagnosis
    • Carcinomas lacking one of these features have been termed "atypical medullary carcinoma" by some
    • We do not use that term, diagnosing them instead as infiltrating ductal carcinoma

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

  • 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
    • Medullary carcinomas are reported to be negative in 90% of cases
  • Her2neu status can be determined by either immunohistology or by FISH
    • The other technique can be used for borderline cases
    • Medullary carcinomas are reported to be negative in 94% of cases
  • Genetics

    • Medullary carcinoma is associated with BRCA1 germ line mutations in a minority of cases, but increased compared to the general population (2 of 18 cases tested)

    Differential Diagnosis

    • Infiltrating ductal carcinoma
      • We designate simply as infiltrating ductal carcinoma those carcinomas that lack any of the five required diagnostic criteria
      • Many of these will be high grade, so the distinction is critical
      • We do not make the diagnosis of atypical medullary carcinoma
    • Large cell lymphoma
      • Lacks syncitial growth pattern and circumscription
      • Can simulate medullary carcinoma because of cytology, lymphoid infiltrate and absence of ducts or glands
      • Immunohistochemistry for lymphoid antigens and keratin can easily resolve this if it is a problem

    Clinical

    • Rare type of carcinoma utilizing strict criteria
    • Early reports indicated a significantly better prognosis than high grade infiltrating ductal carcinoma as long as nodes are negative
      • Some recent studies do not confirm this improved prognosis
      • Problems with interobserver reproducibility and with adherence to strict criteria may explain these variable reports
    • A minority of cases may be associated witih germ line BRCA1 mutations
    • Recurrences are very rare more than 5 years post detection

    Grading / Staging / Report

    Grading

    • Bloom-Scarff-Richardson grading does not apply to medullary carcinoma
      • It is histologically high grade by definition
      • It is clinically low grade as long as the nodes are negative

    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

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    • Fisher ER, Kenny JP, Sass R, Dimitrov NV, Siderits RH, Fisher B. Medullary cancer of the breast revisited. Breast Cancer Res Treat. 1990 Oct;16(3):215-29.
    • Rapin V, Contesso G, Mouriesse H, Bertin F, Lacombe MJ, Piekarski JD, Travagli JP, Gadenne C, Friedman S. Medullary breast carcinoma. A reevaluation of 95 cases of breast cancer with inflammatory stroma. Cancer. 1988 Jun 15;61(12):2503-10.
    • Ridolfi RL, Rosen PP, Port A, Kinne D, Mike V. Medullary carcinoma of the breast: a clinicopathologic study with 10 year follow-up. Cancer. 1977 Oct;40(4):1365-85.
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    • Wargotz ES, Silverberg SG. Medullary carcinoma of the breast: a clinicopathologic study with appraisal of current diagnostic criteria. Hum Pathol. 1988 Nov;19(11):1340-6.
    • Eichhorn JH. Medullary carcinoma, provocative now as then. Semin Diagn Pathol. 2004 Feb;21(1):65-73.
    • Eisinger F, Nogues C, Birnbaum D, Jacquemier J, Sobol H. BRCA1 and medullary breast cancer. JAMA. 1998 Oct 14;280(14):1227-8.
    • Eisinger F, Jacquemier J, Charpin C, Stoppa-Lyonnet D, Bressac-de Paillerets B, Peyrat JP, Longy M, Guinebretiere JM, Sauvan R, Noguchi T, Birnbaum D, Sobol H. Mutations at BRCA1: the medullary breast carcinoma revisited. Cancer Res. 1998 Apr 15;58(8):1588-92.
    • Page DL. Special types of invasive breast cancer, with clinical implications. Am J Surg Pathol. 2003 Jun;27(6):832-5.
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