Phyllodes Tumor

Phyllodes Tumor

Phyllodes tumors were named after their leaf-like architecture characterized by protruding tumor nodules image within a cystic cavity image. These tumors can resemble complex cysts on breast imaging.

The tumor nodules are lined by benign epithelial cells. The characteristic clefts are formed as the stroma becomes more prominent and the spaces separating the epithelial surfaces widen.



  • Phyllodes tumor (PT)


  • Cystosarcoma phyllodes

  • Periductal stromal sarcoma


  • Biphasic tumor consisting of neoplastic intralobular-type stromal cells and benign epithelial cells


Cell of Origin

  • During development of embryo, 1st breast cells to differentiate are stromal cells

    • Stroma induces downgrowth of overlying epithelium to form primitive ducts

    • This molecular cross-talk continues throughout development

  • Neoplastic stromal cells of PT arise from fibroblasts of specialized intralobular stroma

    • Fibroadenomas (FAs) are closely related tumors that also arise from same cells

    • Some FAs are hyperplasias and some neoplasias

    • FA and low-grade PT are on a spectrum of increasing autonomous growth of stromal cells

      • Some PT may arise from a preexisting FA

  • Associated epithelial cells are benign

    • Epithelial cells are stimulated to proliferate by stromal cells

      • In some PTs, epithelial cells have some of the same genetic changes as stromal cells

      • May reflect fact that lobules are derived from a clone of cells

      • In other cases, epithelial cells are polyclonal

      • With very rare exceptions, only stromal cells progress to malignancy

    • With increasing autonomy and growth, stromal cells outgrow epithelial cells

      • High-grade PT may consist almost entirely of stromal cells

    • Only stromal cells are present in distant metastases

DNA Changes

  • Number of chromosomal changes increases with grade of PT

  • Most common changes are gain of 1q and loss of 13, 7p12, 3p24, 10p12, and 9p21

    • Changes are very variable from tumor to tumor

    • Changes are also very variable within tumors

      • Suggests that many subclones with different genetic changes arise during progression

  • Loss of heterozygosity (LOH) is very low in FAs, more common in low- and intermediate-grade PT, and most common in high-grade PT

  • Recurrent PT often gains genetic changes

    • Correlates with increase in histologic grade in ˜ 1/3 of cases

Gene Expression Profiling

  • Patterns of expression vary by PT grade

    • Supports separation into 3 groups

  • Major categories of changes are in genes related to proliferation and stromal/epithelial interactions



  • Incidence

    • Uncommon: < 1% of all breast tumors

  • Age

    • Peak age range for occurrence is 35-55

      • Can occur at any age

  • Ethnicity

    • More common in Asian populations (˜ 7% of breast tumors)


  • Most common presentation is as palpable painless mass

  • Less commonly detected as a density on mammographic screening


  • Surgical approaches

    • Complete excision of all PTs recommended

      • Incomplete excision increases risk for local recurrence

      • Recurrence rates increase from low-grade to high-grade PT; majority occur in 1st 2 years

    • Lower rates of recurrence after mastectomy

  • Adjuvant therapy

    • Chemotherapy has not been shown to be effective

  • Radiation

    • May reduce local recurrence rate

    • Not generally used for initial treatment


  • Difficult to predict

    • Rare and difficult to study

    • Large series from referral centers may not be representative of prognosis in general

    • Treatment is not standardized

  • Outcome can be predicted to some extent by grade of tumor

    • Low-grade PT (also termed “benign”) ˜ 60% of PT

      • Features overlap with cellular FA

      • ˜ 4-10% risk of local recurrence; lower with more extensive surgery

      • < 1% risk of distant metastasis; reported to occur in large series, but these cases have never been described in detail

      • PT can recur at a higher grade; this may explain rare cases with metastasis

    • Intermediate-grade PT (also termed “borderline”) ˜ 10-20% of PT

      • ˜ 20% risk of local recurrence; lower with more extensive surgery

      • < 10% risk of distant metastasis

    • High-grade PT (also termed “malignant”) ˜ 10-20% of PT

      • ˜ 20% risk of local recurrence; lower with more extensive surgery

      • ˜ 30% risk of distant metastasis

Core Needle Biopsy

  • It can be difficult to distinguish PT from FA on core needle biopsies

    • PT can be heterogeneous with some areas having appearance of FA

    • History of recent increase in size favors PT unless patient is pregnant

  • Features favoring PT on core needle biopsy

    • Markedly cellular stroma

    • Invasive border

    • Stromal overgrowth

    • Mitotic rate > 2 per 10 HPF I

      • If 0 or 1, not helpful for distinction

    • Ki-67 > 5%

      • If < 5%, not helpful for distinction

  • If diagnosis is uncertain, best to diagnose “fibroepithelial lesion” and suggest classification after excision


General Features

  • Circumscribed mass

    • May have history of slow or rapid growth

    • Calcifications not usually present

Mammographic Findings

  • Circumscribed mass

  • Partially indistinct margins may be indicative of infiltrative border

Ultrasonographic Findings

  • Usually a hypoechoic mass

    • Internal hyperechoic striations correlate with histologic clefts

    • May have intramural cystic spaces


General Features

  • Typically well-defined lobulated masses with bosselated borders

    • Higher grade PT may show tongues of tumor protruding into adjacent breast parenchyma

  • May show cleft-like cystic spaces


  • Most often 4-8 cm (range: 1-40 cm)

Sections to Be Submitted

  • PT can be very heterogeneous

    • High-grade features or malignant heterologous elements may be focal

    • Epithelial component may be focal in high-grade lesions

  • Tumors should be sampled with at least 1 section per cm of greatest size

    • Preferable to completely sample PT when possible

  • Margins should be extensively sampled if undergoing breast-conserving therapy


Histologic Features

  • Diagnosis of PT requires presence of both spindle stromal cells and benign epithelium

  • Characteristics of stromal cells are used to distinguish PT from FA and for classification

    • Cellularity can vary from paucicellular to highly cellular areas

      • In very cellular areas, cells are organized in parallel arrays (fascicles)

      • Condensation (increased cellularity) is often found adjacent to epithelium (“cambium” layer)

    • Stromal overgrowth

      • Areas of stroma that lack a benign epithelial component (at least 1 HPF)

      • Does not include paucicellular hyalinized areas

      • More common in higher grade tumors; uncommon or absent in FAs

    • Nuclear pleomorphism

      • Usually mild or moderate

      • Markedly pleomorphic nuclei are only seen in high-grade PT

      • Does not include scattered multinucleated cells that may be degenerative in nature

    • Mitotic rate

      • Majority of PT will have at least some mitoses

      • Mitoses in epithelial component are not used for classification

    • Infiltrative border

      • Higher grade PT can invade into surrounding breast tissue, creating an irregular border

      • FA and low-grade PT have pushing circumscribed borders

      • Must be distinguished from fibroadenomatoid changes in adjacent tissue

      • Adipose tissue within a PT is usually an indication of invasion; liposarcoma must also be considered

    • Heterologous elements

      • Liposarcoma, chondrosarcoma, osteosarcoma, and rhabdomyosarcoma can occur in PT

      • More common as part of PT than as primary sarcomas

      • Extensive sampling may be necessary to identify benign epithelium diagnostic of PT

    • Growth pattern

Jul 6, 2016 | Posted by in PATHOLOGY & LABORATORY MEDICINE | Comments Off on Phyllodes Tumor

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