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Surgical Pathology Criteria
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Pure Mucinous Carcinoma of the Breast

Definition

  • A breast carcinoma of which at least one third of the volume of the tumor is extracellular mucin throughout
    • Invasion is in the form of pools of stromal mucin containing neoplastic cells

Diagnostic Criteria

  • Pools of extracellular mucin make up at least one third of volume throughout
    • If focal areas are not at least 33% mucinous, designate as mixed mucinous/ductal
      • i.e. if only some areas are 33% mucinous, call it mixed
    • If mucin does not attain 33% threshhold in any area, designate as infiltrating ductal carcinoma with mucinous differentiation
      • i.e. if no area makes it to 33% mucinuos, call it carcinoma with mucinous differentiation
  • Detached epithelial elements present floating in the mucin
    • May be trabecular, cribriform, micropapillary, sheet like or clumps
  • No areas of the usual type of invasion of stroma in the absence of mucin
    • If present, designate as mixed mucinous/ductal
  • Usually low grade cytology
    • May have any higher grade of atypia
    • Must have at least the cytologic features of the cells of low grade ductal carcinoma in situ
      • Must not be cytologically identical to normal cells
  • In situ component may be present
  • May be seen in association with neuroendocrine differentiation
  • Should always be diagnosed with the qualifier "pure" or "mixed"

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

Differential Diagnosis

A number of low grade or benign lesions are characterized by pools of mucin
Mucinous DCIS Extracellular, intralumenal mucin in a duct lined by DCIS, no mucin in contact with stroma
DCIS with mucocele-like lesion Typical DCIS with discrete areas of rupture resulting in mucin pools in stroma, no groups of cells floating in mucin
ADH with mucocele-like lesion Some but not all features required for diagnosis of DCIS with discrete areas of rupture resulting in mucin pools in stroma, no groups of cells floating in mucin
Mucocele-like lesion Pools of mucin in stroma variably lined by bland epithelium, usually no groups of cells floating in mucin (if present they are normal ductal cells and are not complex), almost always a microscopic lesion
Mucinous carcinoma Mucin in contact with stroma, neoplastic cells floating in mucin
Nodular mucinosis Nodules of stromal mucin, no epithelial component, subareolar

Mucinous Carcinoma vs. Signet Ring Carcinoma

  • Mucinous carcinomas are characterized by cells floating in pools of mucin
  • Signet ring carcinomas are characterized by cells with intracellular mucin that indents the nucleus
  • Signet ring cells can be found in otherwise mucinous carcinomas
    • If at least 20% of cells are signet ring, designate as signet ring carcinoma
      • Prognosis is that of usual infiltrating carcinoma of identical grade
      • Signet ring carcinoma is usually a variant pattern of lobular carcinoma
    • If <20% of cells are signet ring, designate as mucinous carcinoma with signet ring cells
      • Prognosis may not be worse than pure mucinous carcinoma

Clinical

  • Ten year survival approximately 85%
  • Lymph node metastases are rare from pure low grade mucinous carcinoma, almost never if under 2 cm diameter
  • Lymph node metastases reported in 15-20% of cases, but many of these may be mixed mucinous/ductal cases
  • If metastases are present, review primary for evidence of another pattern

Grading / Staging / Report

Grading

  • Usually low grade cytology but all degrees of atypia may be found

  • 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

  • In the context of mucinous carcinoma, the presence of mucin in a margin constitutes involvement by carcinoma

  • 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

  • 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.
  • Andre S, Cunha F, Bernardo M, Meneses e Sousa J, Cortez F, Soares J. Mucinous carcinoma of the breast: a pathologic study of 82 cases. J Surg Oncol. 1995 Mar;58(3):162-7.
  • Clayton F. Pure mucinous carcinomas of breast: morphologic features and prognostic correlates. Hum Pathol. 1986 Jan;17(1):34-8.
  • Coady AT, Shousha S, Dawson PM, Moss M, James KR, Bull TB. Mucinous carcinoma of the breast: further characterization of its three subtypes. Histopathology. 1989 Dec;15(6):617-26.
  • Fisher ER, Palekar AS, Stoner F, Constantino J. Mucocele-like lesions and mucinous carcinoma of the breast. 1994; Int J Surg Pathol 1:213-20.
  • Maluf HM, Koerner FC. Solid papillary carcinoma of the breast. A form of intraductal carcinoma with endocrine differentiation frequently associated with mucinous carcinoma. Am J Surg Pathol. 1995 Nov;19(11):1237-44.
  • Merino MJ, Livolsi VA. Signet ring carcinoma of the female breast: a clinicopathologic analysis of 24 cases. Cancer. 1981 Oct 15;48(8):1830-7.
  • Norris HJ, Taylor HB. Prognosis of mucinous (gelatinous) carcinoma of the breast. Cancer. 1965 Jul;18:879-85.
  • Rasmussen BB, Rose C, Christensen IB. Prognostic factors in primary mucinous breast carcinoma. Am J Clin Pathol. 1987 Feb;87(2):155-60.
  • Ro JY, Sneige N, Sahin AA, Silva EG, del Junco GW, Ayala AG. Mucocelelike tumor of the breast associated with atypical ductal hyperplasia or mucinous carcinoma. A clinicopathologic study of seven cases. Arch Pathol Lab Med. 1991 Feb;115(2):137-40.
  • Rosen PP. Mucocele-like tumors of the breast. Am J Surg Pathol. 1986 Jul;10(7):464-9.
  • Rosen PP, Wang TY. Colloid carcinoma of teh breast: Analysis of 64 patients with long-term follow-up. 1980; Am J CLin Pathol 73:304.
  • Scopsi L, Andreola S, Pilotti S, Bufalino R, Baldini MT, Testori A, Rilke F. Mucinous carcinoma of the breast. A clinicopathologic, histochemical, and immunocytochemical study with special reference to neuroendocrine differentiation. Am J Surg Pathol. 1994 Jul;18(7):702-11.
  • 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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