Breast
Other carcinoma subtypes, WHO classified
Micropapillary


Minor changes: 10 September 2020

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PubMed search: Micropapillary carcinoma[TI] breast "free full text"[sb]

Ruhani Sardana, M.B.B.S.
Kamaljeet Singh, M.D.
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Cite this page: Sardana R, Singh K. Micropapillary. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignantmicropapillary.html. Accessed October 24th, 2020.
Definition / general
Essential features
  • Pseudopapillae, morulae or tubules with inside out growth pattern characterized by reverse polarity of cells
Terminology
  • Invasive micropapillary carcinoma: > 90% of invasive component consists of micropapillary carcinoma
  • Invasive breast carcinoma with micropapillary component: micropapillary pattern is present in association with other histologic types (more common)
Epidemiology
  • < 2 - 8% of all breast cancers (Mod Pathol 2018;31:956)
  • Pure micropapillary carcinoma is rare, 0.9 - 2% of all breast cancers; often admixed with other histologic subtypes
  • Reported median age: 50 - 62 years
  • Mean age: 59 years; range: 25 - 92 years
  • Also described in male breast (Breast Care 2018;13:192)
Sites
  • Breast parenchyma
Pathophysiology
Etiology
  • Unknown
Clinical features
  • Almost 90% present as a palpable mass
  • Radiologic findings, locations and gross features similar to conventional invasive breast carcinoma (BMC Cancer 2017;17:839)
  • Aggressive clinical presentation with large tumor size (often T2), frequent positive lymph nodes at initial presentation and advanced stage when compared with invasive ductal carcinoma (Cancer Med 2017;6:2775)
  • Mean size: 1.5 - 3.9 cm
  • Frequent and higher number of axillary nodal metastasis (44 - 85%) at initial diagnosis
Diagnosis
  • Tissue biopsy or surgical resection
Radiology description
  • Multiple lesions, accompanying nonmass enhancement and axillary lymph node enlargement
  • Irregular spiculated mass on mammogram
  • Irregular hypoechoic mass with spiculated margins and posterior acoustic shadowing on ultrasound
  • Irregular mass with washout kinetics and diffuse heterogeneous mass-like enhancement in MRI
  • Radiologists to consider axillary sonography if this entity is found in a core needle biopsy specimen (AJR Am J Roentgenol 2013;200:689)
Prognostic factors
  • Traditionally, presence of micropapillary carcinoma component has been considered a poor prognostic factor; however, the data has been controversial
  • Meta analysis of 14 published studies showed that presence of micropapillary carcinoma histology is an unfavorable prognostic factor for recurrence free survival and locoregional recurrence free survival (BMC Cancer 2017;17:839)
Case reports
Treatment
  • Tumors are typically ER positive and are eligible for antiestrogen treatment
  • Treatment varies depending on clinical stage (tumor size and lymph node metastasis)
Gross description
  • No specific gross features; tumors with > 50% of micropapillary growth tend to be larger (mean: 6 cm) than those with lesser amount of this pattern (mean: 3.5 cm)
  • Mean tumor size: 2 cm; range: 0.1 - 10 cm
  • Lobulated outline
Microscopic (histologic) description
  • Tufts of cells arranged in pseudopapillae, hollow tubules and morula that are surrounded by empty clear spaces formed by fibrocollagenous stroma (Arch Pathol Lab Med 2016;140:799)
  • Cells show characteristic reverse polarity, also called inside out pattern, with apical surface abutting the epithelial stromal interface
  • Densely cellular, with minimal stroma
  • Abundant eosinophilic cytoplasm
  • Nuclei around the periphery bulge with knobby / serrated appearance
  • Extensive true angiolymphatic invasion (78%)
  • Foci of necrosis may be present
  • May have intracytoplasmic mucin
  • Uncommon variant feature: psammoma bodies, microcystic dilation of lumens with cell clusters, apocrine differentiation, multinucleated giant cells (e.g. osteoclast)
  • Variable histologic grade, usually grade 2 or 3
  • Mucinous carcinoma can contain micropapillary component, also called mucinous micropapillary carcinoma
Microscopic (histologic) images

Contributed by Kamaljeet Singh, M.D.
Micropapillary carcinoma Micropapillary carcinoma Micropapillary carcinoma

Micropapillary carcinoma

Lymphovascular invasion

Lymphovascular invasion

EMA

EMA

E-cadherin

E-cadherin


p120

p120

HER2 2+

HER2 2+

HER2 3+

HER2 3+

Mucinous micropapillary carcinoma Mucinous micropapillary carcinoma Mucinous micropapillary carcinoma

Mucinous micropapillary carcinoma


Mucinous hypercellular tumor

Mucinous hypercellular tumor

HER2+ mucinous micropapillary carcinoma

HER2+ mucinous micropapillary carcinoma

Cytology description
  • Increased cellularity, angulated clusters, abortive papillae and isolated malignant cells
  • Staghorn epithelial structures in 35%, giving serrated border (Pathology 2007;39:401)
  • May have few malignant appearing multinucleated giant cells or focal mucin (Acta Cytol 2009;53:463)
  • No fibrovascular cores (Cancer 2002;96:280)
Positive stains
Electron microscopy description
  • Microvilli on their cell membranes lining the outer surfaces of the cell clusters
  • Secretory activity in stroma facing surface of tumor cells
Molecular / cytogenetics description
Sample pathology report
  • Breast, right, 12:00 mass, core needle biopsy:
    • Invasive breast carcinoma with micropapillary component, histologic grade 2, measuring 1.5 cm in greatest length
    • Lymphovascular invasion is present (see comment)
    • Comment: The sample shows a moderately differentiated carcinoma comprised of invasive ductal carcinoma and micropapillary carcinoma components. The tumor is ER positive (90%; 3+), PR positive (50%; 3+) and HER2 equivocal by IHC (score 2+).
Differential diagnosis
Board review style question #1

Which of the following is true regarding micropapillary carcinoma of breast?

  1. Low stage disease is typical presentation
  2. Pure micropapillary carcinoma is common
  3. Tumor cells show circumferential HER2 staining
  4. Tumor cells show inside out pattern with EMA immunostaining
  5. Tumor is frequently ER negative
Board review answer #1
D. Tumor cells show inside out pattern with EMA immunostaining. Micropapillary pattern is frequently present as a component of a larger invasive breast carcinoma. Tumor is frequently ER positive and tumor cells show cup shaped basolateral HER2 immunostaining. Tumors often present at high stage with high number of lymph node involvement. Tumor cells show reverse polarity, also known as inside out pattern with apical surface placed towards the stroma. Inside out pattern can be demonstrated by EMA staining of the apical surface.

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Reference: Micropapillary carcinoma
Board review style question #2
The HER2 immunohistochemical staining pattern of tumor cells in micropapillary carcinoma is

  1. Apical
  2. Basal
  3. Circumferential
  4. Cup shaped basolateral
  5. Cytoplasmic
Board review answer #2
D. Cup shaped basolateral. The basal and lateral surfaces of the tumor cells show membranous staining (cup shaped). No staining is noted on the apical surface that stains with EMA.

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Reference: Micropapillary carcinoma
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