Phyllodes Tumor of Breast: Epidemiology, Etiology, Pathogenesis, Classification, Histopathology, Symptoms, Diagnosis, Management and Prevention

Phyllodes Tumor of the Breast

~Introduction

Phyllodes tumor is a rare fibroepithelial neoplasm of the breast characterized by a distinctive leaf-like (phyllodes) growth pattern. The term “phyllodes” is derived from the Greek word phyllon, meaning “leaf,” which describes the tumor’s histological appearance. These tumors account for less than 1% of all breast neoplasms and approximately 2–3% of fibroepithelial breast tumors.

Phyllodes tumors show a wide spectrum of biological behavior ranging from benign lesions to aggressive malignant tumors with metastatic potential. Due to their rarity, variable presentation, and overlap with fibroadenomas, diagnosis and management remain challenging. Early recognition and appropriate surgical treatment are essential to prevent recurrence and complications.

~Historical Background

Phyllodes tumor was first described by Johannes Müller in 1838 as cystosarcoma phyllodes. The term was misleading because most tumors are not cystic, nor are they sarcomas. The World Health Organization (WHO) later replaced the term with “phyllodes tumor” to better reflect its true pathological nature.

~Epidemiology

• Phyllodes tumors are uncommon.

• They occur predominantly in women aged 35–55 years, about a decade later than fibroadenomas.

• Rare cases have been reported in adolescents and elderly women.

• Incidence is slightly higher in Asian and Latin American populations.

• Male cases are extremely rare and usually associated with gynecomastia.

~Etiology and Risk Factors

The exact cause of phyllodes tumors is unknown. However, several factors have been implicated:

• Hormonal influences, especially estrogen

• Prior history of fibroadenoma

• Genetic alterations involving MED12 mutations

• Increased stromal responsiveness to growth factors

• Trauma or previous breast surgery (rare association)

~Pathogenesis

Phyllodes tumors arise from the periductal stromal cells of the breast. Unlike fibroadenomas, which have a balanced epithelial and stromal component, phyllodes tumors show stromal overgrowth, which determines their biological behavior.

The tumor grows rapidly due to:

• Increased stromal cellularity

• Enhanced mitotic activity

• Abnormal stromal-epithelial interactions

~Classification

According to the WHO classification, phyllodes tumors are divided into three categories based on histological features:

1. Benign Phyllodes Tumor

• Mild stromal cellularity

• Minimal atypia

• Low mitotic activity (<5 per 10 HPF)

• Well-defined margins

• Rare recurrence

2. Borderline Phyllodes Tumor

• Moderate stromal cellularity

• Mild to moderate atypia

• Mitotic rate 5–9 per 10 HPF

• Focal infiltrative margins

• Intermediate recurrence risk

3. Malignant Phyllodes Tumor

• Marked stromal cellularity

• Severe atypia

• High mitotic rate (≥10 per 10 HPF)

• Stromal overgrowth

• Infiltrative margins

• Risk of distant metastasis

~Gross Pathology

• Tumors are typically large, ranging from 3 cm to more than 20 cm

• Well-circumscribed but may be lobulated

• Cut surface shows:

  • Gray-white appearance

  • Slit-like cystic spaces

  • Leaf-like projections into clefts

• Hemorrhage and necrosis may be seen in malignant tumors

~Histopathology

Microscopic Features

• Biphasic tumor composed of:

  • Epithelial component (benign ductal epithelium)

  • Stromal component (neoplastic)

• Characteristic leaf-like architecture

• Stromal features determine tumor grade:

  • Cellularity

  • Atypia

  • Mitotic figures

  • Stromal overgrowth

  • Tumor margins

Immunohistochemistry

• Stromal cells may express:

  • CD34

  • Vimentin

• Malignant tumors may show:

  • p53 overexpression

  • High Ki-67 index

~Clinical Features

Presenting Symptoms

• Painless, rapidly growing breast lump

• Usually unilateral

• Skin stretching or ulceration in large tumors

• Nipple retraction is uncommon

• Axillary lymphadenopathy is rare

Growth Pattern

• Rapid enlargement over weeks to months

• Faster growth compared to fibroadenomas

~Radiological Features

Mammography

• Well-defined or lobulated mass

• May resemble fibroadenoma

• Large size raises suspicion

Ultrasound

• Solid, hypoechoic mass

• Cystic spaces within tumor

• Increased vascularity

MRI

• Useful in large or recurrent tumors

• Demonstrates heterogeneity and stromal overgrowth

~Differential Diagnosis

• Fibroadenoma

• Breast sarcoma

• Metaplastic carcinoma

• Giant fibroadenoma

• Invasive ductal carcinoma (rare mimic)

~Diagnosis

Core Needle Biopsy

• Preferred diagnostic method

• Allows assessment of stromal cellularity and mitosis

• Distinction between fibroadenoma and phyllodes tumor may be difficult

Excision Biopsy

• Often required for definitive diagnosis

• Histological grading performed on excised specimen

~Management

Surgical Treatment

Surgery is the mainstay of treatment.

Wide Local Excision

• Recommended for all grades

• Margin of at least 1 cm

• Reduces local recurrence

Mastectomy

• Indicated for:

  • Very large tumors

  • Recurrent tumors

  • Tumors not amenable to breast-conserving surgery

Axillary Surgery

• Not routinely indicated

• Lymph node metastasis is rare

Adjuvant Therapy

Radiotherapy

• Considered in:

  • Malignant phyllodes tumors

  • Recurrent disease

  • Close or positive margins

• Reduces local recurrence

Chemotherapy

• Limited role

• Used in metastatic malignant phyllodes tumors

• Regimens similar to soft tissue sarcomas

~Prognosis

Prognosis depends on tumor grade and surgical margins.

Tumor Type	Local Recurrence	Metastasis
Benign	10–17%	Rare
Borderline	14–25%	Low
Malignant	23–30%	10–20%

Common metastatic sites:

• Lungs

• Bone

• Liver

• Brain (rare)

~Recurrence

• Usually occurs within 2–3 years

• More common with:

  • Inadequate margins

  • High-grade tumors

• Recurrent tumors may show higher grade

~Special Situations

Phyllodes Tumor in Pregnancy

• Rare

• Hormonal influence may accelerate growth

• Managed surgically

Giant Phyllodes Tumor

• Tumors >10 cm

• Can cause ulceration and bleeding

• Often require mastectomy

~Molecular and Genetic Aspects

• MED12 mutations common

• Alterations in:

  • TP53

  • EGFR

  • RB1

• Ongoing research may help targeted therapy in future

~Prevention and Screening

• No specific preventive measures

• Early evaluation of rapidly growing breast lumps

• Regular follow-up after treatment

~Conclusion

Phyllodes tumor is a rare but important breast neoplasm with diverse biological behavior. Accurate diagnosis requires careful histopathological evaluation, and complete surgical excision with adequate margins is the cornerstone of treatment. Although most phyllodes tumors are benign, malignant variants can metastasize and carry significant morbidity. Long-term follow-up is essential due to the risk of recurrence. Advances in molecular pathology may offer new insights into targeted therapy in the future.