Definition/General

Introduction:
-Phyllodes tumor of ovary is an exceptionally rare entity with fewer than 50 cases reported worldwide
-Most represent metastatic phyllodes tumor from breast rather than primary ovarian tumors
-Primary ovarian phyllodes tumors are biphasic neoplasms composed of epithelial and stromal components with leaf-like architecture similar to breast counterparts.
Origin:
-Primary ovarian phyllodes tumors likely arise from ovarian stroma or teratomatous elements within ovarian teratomas
-Metastatic cases result from hematogenous spread from breast phyllodes tumors
-The biphasic nature suggests origin from pluripotent mesenchymal cells capable of both epithelial and stromal differentiation
-Malignant transformation occurs in stromal component.
Classification:
-WHO 2020 does not specifically recognize primary ovarian phyllodes tumor
-Classification borrowed from breast: Benign phyllodes tumor - low stromal cellularity, no atypia
-Borderline phyllodes tumor - moderate stromal cellularity, mild atypia
-Malignant phyllodes tumor - high stromal cellularity, marked atypia, >10 mitoses/10 HPF
-Metastatic phyllodes tumor - usually malignant type.
Epidemiology:
-Extremely rare - fewer than 50 cases in literature
-Age range 20-60 years (mean 40 years)
-Younger age than typical ovarian carcinomas
-No racial predilection reported
-Indian population - no documented cases in literature
-Bilateral involvement extremely rare (suggests metastatic disease)
-Associated with ovarian teratomas in 30% primary cases.

Clinical Features

Presentation:
-Unilateral pelvic mass (90% cases) with rapid enlargement
-Abdominal distension due to large tumor size
-Pelvic pressure symptoms
-Asymptomatic in 30% cases (incidental finding)
-History of breast phyllodes tumor should be sought
-No specific tumor markers elevated
-Young age at presentation compared to other ovarian malignancies.
Symptoms:
-Pelvic/abdominal pain (60% cases) due to mass effect
-Abdominal distension and bloating (50% cases)
-Urinary frequency from pelvic pressure (30% cases)
-Menstrual irregularities in premenopausal women (25% cases)
-Constitutional symptoms rare unless malignant transformation
-Rapid tumor growth may cause acute symptoms
-No specific constitutional symptoms typical.
Risk Factors:
-No established risk factors for primary ovarian phyllodes tumor
-History of breast phyllodes tumor increases risk of ovarian metastases
-History of ovarian teratoma (30% association with primary cases)
-Young reproductive age
-No genetic predisposition identified
-No hormonal associations reported
-Previous malignant phyllodes tumor of breast highest risk factor.
Screening:
-No specific screening due to extreme rarity
-Patients with breast phyllodes tumor should have regular pelvic examinations
-Pelvic ultrasound for pelvic masses
-MRI for detailed characterization
-No effective tumor markers
-CT chest/abdomen/pelvis if metastatic disease suspected
-Regular follow-up after breast phyllodes tumor treatment.

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Gross Description

Appearance:
-Tumors typically large size measuring 10-25 cm in greatest dimension
-Cut surface shows characteristic leaf-like architecture with slit-like spaces lined by epithelium and intervening stromal tissue
-Surface may be smooth or bosselated
-Cystic and solid areas present with variable hemorrhage and necrosis in malignant cases.
Characteristics:
-Firm to soft consistency depending on stromal/epithelial ratio
-Color ranges from gray-white to tan-pink
-Leaf-like papillary projections protruding into cystic spaces are pathognomonic
-Fleshy, fish-flesh appearance similar to breast phyllodes tumors
-Necrosis and hemorrhage in malignant variants
-Calcifications may be present.
Size Location:
-Size ranges from 8-30 cm (median 15 cm) - typically larger than breast counterparts
-Unilateral involvement in >95% cases (bilateral suggests metastatic disease)
-Usually replaces entire ovary with residual normal ovarian tissue at periphery
-May show capsular extension and involvement of adjacent structures in malignant cases.
Multifocality:
-Bilateral involvement extremely rare (<5%) and suggests metastatic disease from breast
-Peritoneal implants may occur in malignant phyllodes tumor
-Hematogenous metastases to lungs, liver, and bone in advanced malignant cases
-Lymph node involvement rare even in malignant cases
-Local recurrence if incompletely excised.

Microscopic Description

Histological Features:
-Biphasic tumor composed of epithelial and stromal components
-Leaf-like architecture with cleft-like spaces lined by benign epithelium and hypercellular stroma
-Stromal component shows variable cellularity and may contain heterologous elements (cartilage, bone, fat)
-Epithelial component typically benign, cuboidal to columnar.
Cellular Characteristics:
-Epithelial cells: Benign appearance with uniform nuclei and minimal mitotic activity
-Stromal cells: Spindle-shaped cells with variable cellularity and atypia
-In benign phyllodes - uniform spindle cells with minimal atypia
-In malignant phyllodes - marked nuclear pleomorphism with bizarre cells and high mitotic activity (>10/10 HPF).
Architectural Patterns:
-Intracanalicular pattern - stromal tissue compresses epithelial elements into slit-like spaces
-Pericanalicular pattern - stroma surrounds round epithelial spaces
-Leaf-like projections with epithelial lining and stromal cores
-Solid areas of hypercellular stroma in malignant cases
-Heterologous differentiation (malignant cartilage, bone) in some cases.
Grading Criteria:
-Benign: <2 mitoses/10 HPF, minimal stromal cellularity, no nuclear atypia, pushing margins
-Borderline: 2-9 mitoses/10 HPF, moderate stromal cellularity, mild atypia
-Malignant: ≥10 mitoses/10 HPF, high stromal cellularity, marked atypia, infiltrative margins
-Overgrowth of stromal component (4x magnification field without epithelium) indicates malignancy.

Immunohistochemistry

Positive Markers:
-Stromal component: CD34 (variable, 60%), Vimentin (95%), SMA (focal, 30%), CD10 (70%)
-Epithelial component: CK7 (90%), EMA (85%), CK19 (80%)
-In malignant areas: p53 may be positive (40%), Ki-67 high (>20%)
-Estrogen receptor may be positive in stromal component (50%).
Negative Markers:
-Stromal component: Desmin typically negative, CD117 negative, DOG1 negative
-Epithelial component: CK20 negative, TTF-1 negative, CDX2 negative
-Inhibin negative, Calretinin negative (excludes sex cord-stromal tumors)
-S-100 negative in most cases.
Diagnostic Utility:
-IHC pattern similar to breast phyllodes tumor - helpful in confirming metastatic origin
-CD34 positivity in stromal component supports phyllodes tumor diagnosis
-CK7+/CK20- pattern in epithelial component
-Absence of specific ovarian markers (WT1, inhibin) helps exclude primary ovarian tumors
-p53 and Ki-67 aid in grading.
Molecular Subtypes:
-Limited molecular data available due to rarity
-Similar molecular profile to breast phyllodes tumors suggested
-MED12 mutations (common in breast phyllodes) not well-studied in ovarian cases
-TERT promoter mutations may be present in malignant cases
-PIK3CA mutations reported in some cases
-Chromosomal instability increases with grade.

Molecular/Genetic

Genetic Mutations:
-Limited data due to extreme rarity
-MED12 mutations theoretically possible (common in breast phyllodes)
-TP53 mutations in malignant transformation (30% of malignant cases)
-PIK3CA mutations reported in few cases (20%)
-CDKN2A/B deletions in high-grade cases
-MYC amplification may occur in sarcomatous areas.
Molecular Markers:
-p53 expression pattern correlates with TP53 mutation status and prognosis
-Ki-67 proliferation index increases with grade (benign <5%, malignant >20%)
-CD34 expression may decrease in malignant transformation
-MDM2 amplification possible in malignant cases
-PDGFRA expression in stromal component.
Prognostic Significance:
-Tumor grade most important prognostic factor - malignant phyllodes has poor prognosis with 5-year survival <50%
-Complete excision critical - positive margins increase recurrence risk
-Size >10 cm associated with worse outcome
-TP53 mutations predict aggressive behavior
-High Ki-67 (>30%) indicates poor prognosis.
Therapeutic Targets:
-Limited therapeutic options due to rarity
-Complete surgical excision is primary treatment
-Chemotherapy efficacy limited - doxorubicin-based regimens for malignant cases
-Radiation therapy for local control in unresectable cases
-Targeted therapy under investigation - CDK4/6 inhibitors, anti-angiogenic agents
-Immunotherapy limited data available.

Differential Diagnosis

Similar Entities: Ovarian sarcoma (lacks biphasic pattern), carcinosarcoma/MMMT (malignant epithelial component), teratoma with sarcomatous transformation, metastatic sarcoma, sex cord-stromal tumors (different IHC profile), primary ovarian carcinoma with sarcomatoid features.
Distinguishing Features:
-Ovarian sarcoma: Purely mesenchymal, lacks epithelial component
-Carcinosarcoma: Malignant epithelial component, different IHC
-Teratoma: Mature elements, lacks leaf-like architecture
-Sex cord tumors: Inhibin+, different morphology
-Sarcomatoid carcinoma: Malignant epithelial areas, cytokeratin positive throughout.
Diagnostic Challenges:
-Distinguishing primary vs metastatic - clinical history of breast lesion crucial
-Limited sampling may not show characteristic leaf-like pattern
-Malignant phyllodes vs sarcoma - requires identification of benign epithelial component
-Grading difficulties - subjective assessment of stromal cellularity and atypia.
Rare Variants:
-Phyllodes tumor with heterologous elements - contains cartilage, bone, fat, or striated muscle
-Epithelial-predominant variant - prominent epithelial component may obscure stromal features
-Adenosarcoma-like areas - may show overlap with Mullerian adenosarcoma
-Liposarcomatous differentiation - malignant adipocytes in stromal component.

Sample Pathology Report

Template Format

Sample Pathology Report

Complete Report: This is an example of how the final pathology report should be structured for this condition.

Specimen Information

Right/Left ovary and fallopian tube, total weight: __ grams. Ovary measures __ x __ x __ cm, markedly enlarged. External surface smooth/bosselated. Cut surface shows characteristic leaf-like architecture with slit-like spaces and intervening stromal tissue. Areas of necrosis/hemorrhage present/absent.

Diagnosis

Phyllodes tumor, __ type (benign/borderline/malignant), with the following features: Leaf-like architecture, stromal cellularity __ (low/moderate/high), nuclear atypia __ (minimal/mild/marked), mitotic rate __ per 10 HPF, stromal overgrowth present/absent.

Final Diagnosis

PHYLLODES TUMOR OF OVARY, __ TYPE (Benign/Borderline/Malignant)\n\nSize: __ cm\nMargins: Negative/Positive\nStromal mitoses: __ per 10 HPF\nStromal atypia: Minimal/Mild/Marked\n\nIHC Profile: CD34 (stromal, +/-), CK7 (epithelial, +), p53 (__), Ki-67 (__%)\n\nNote: PRIMARY vs METASTATIC phyllodes tumor - Clinical correlation with breast imaging/history essential. Multidisciplinary team discussion recommended for treatment planning.