gestational trophoblastic diseases · placental site trophoblastic tumor simulating carcinoma. am j...
TRANSCRIPT
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Gestational Trophoblastic Diseases
The common and the Rare
Guangming Han MD FRCPC
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Gestational Trophoblastic Disease
• Molar
• Non-Molar
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A Common Question
• The villi in this P.O.C. seem a bit edematous and there are some (maybe?) trophoblastic proliferation. Is it a molar pregnancy?
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CLASSICAL COMPLETE MOLE
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EARLY COMPLETE MOLE
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PARTIAL MOLE
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HYDROPIC ABORTUS
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ECM CM PM HA
Trophoblast Proliferation
++ ++++ + -
Villi Spectrum sizes
Spectrum sizes
2 populations Balloon-like
Scalloped villous contours
Uncommon Uncommon + Rare
Club-like projections
+ -/+ Rare Rare
Cisterns
Variable Prominent Variable Absent/rare
Pseudoinclusion + + + -
Karyorrhexis +++ -/+ -/+ -/+
Fetal tissue - - + -
Persistent GTD 10-30% 10-30% 0.5-1 % -
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Ancillary tests
• P57 immunohistochemistry • Ploidy analysis
– Traditional karyotyping – Flow cytometry – FISH
• Short tandem repeat (STR) genotyping
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Hydatidiform Mole
OR
COMPLETE MOLE
ANDROGENETIC (DIANDRIC DIPLOID) 46XX
46XY
80% 20%
PARTIAL MOLE 90% 10%
Monospermy with reduplication or Tetraploid
DIANDRIC MONOGYNIC TRIPLOID 69XXY
69XYY 69XXX
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p57
Complete mole Most likely not a complete mole
Negative in cytotrophoblast Negative in stromal cells
PATERNALLY IMPRINTED (MATERNALLY EXPRESSED)
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NON MOLAR (Biparental Diploidy)
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Monospermic Androgenetic Diploidy
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Diandric Triploid: Partial Hydatidiform Mole
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Abnormal P57 results: Discordant P57 expression in androgenetic biparental diploidy mosaic/chirmaric conception CM with aberrant P57 expression - androgenetic diploidy with retained maternal chromosome 11
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Androgenetic Diploid with Retention of Maternal Chr 11 (p57 positive CHM)
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Potential Pitfalls
• Twin pregnancy • Mosaic/chimeric conceptions • Biparental CM • Egg donor gestation
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Morphologically suspicious for hydatitiform mole
P57 Immunohistochemistry
P57 Negative P57 Positive, equivocal, aberrant , discordant
Morphology yes
Morphology equivocal Molecular genotyping
Diandric diploidy
Diandric triploidy
Digynic triploidy
Biparental diploidy
Trisomy or monosomy
CM PM Non-molar
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A Common Question
• There is something looks like trophoblastic, do I need to worry about it?
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CASE 1
27 F G2P2 Plateau of hCG = 27-30, several months after pregnancy Spotting ?Mild dilation of cornua on ultrasound
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CASE 2
34 F G4P4 Spotting 12 months following last pregnancy No hCG elevation
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CASE 3
34 F G4P3A1(aborted a complete hydatidiform mole) Spotting 6 months following evacuation Low level elevations of hCG: 17
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p63
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Ki-67
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CASE 4
28F G1P1 (normal baby girl) 2 years post delivery: spotting and microscopic hematuria hCG: 104; ultrasound normal
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Ki-67
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Case 5
• 48-year-old woman • G2P0 • Vaginal bleeding, nausea, and increase in
breast size • Serum beta-hCG: 435,915 • D&C
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History Con’t
• Rising serum beta-hCG post D&C • Treatment:
– Methotrexate and leucovorin – TAH-BSO
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History Con’t
• Chemotherapy • Patient was followed for the next 6 years • An elevated serum beta-hCG (30.1) was noted
on routine follow up • CT: a 0.7 cm nodule in the upper lobe of the
left lung • Wedge lung resection
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hPL
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CD10
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CK18
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Inhibin
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p63
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Ki-67
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Epithelioid Trophoblastic Tumor
A tumor composed of chorionic-type intermediate trophoblastic cells
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Epithelioid Trophoblastic Tumor
• Majority are uterine or cervical primaries • Pregnancy or GTD history
– Variable, can be remote
• History of mole – 14%
• Serum hCG: low (<2,000 mIU/ml) • Behavior: Self-limited, persistent, or aggressive • Response to Chemo: variable
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Epithelioid Trophoblastic Tumor
• Reported pulmonary primaries - rare
Lewin SN et al. 2009, Am J Surg Pathol 33:1809 - 1814
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Differential Diagnosis • Squamous cell carcinoma of the cervix
• Primary lung carcinoma
– Squamous cell carcinoma – Pleomorphic carcinoma – Other carcinomas with trophoblasts
• Primary or metastatic germ cell tumor with trophoblastic
differentiation
• Other gestational trophoblastic tumors
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Squamous Cell Carcinoma
Resemble ETT
• Clinical features
• Pathologic features
• Immunohistochemistry
Different from ETT
• Location – Cervical/lower uterine
segment – Lung
• Morphology – Epithelioid with pink
cytoplasm – Necrosis
• P63 positive
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Immunohistochemistry
ETT Squamous cell carcinoma
P63 + +
CK5/6 - or focal +
P16 - + (in HPV associated cervical SCC)
Inhibin + 20%
CD10 + 20%
HSD3B1 + -
hPL +/- -
Mel-CAM +/- -
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Pleomorphic Carcinoma
Resemble ETT
• Polygonal cells with eosinophilic cytoplasm
• Large multinucleated cells
Different from ETT • Neutrophilic infiltrate,
sometime within the cytoplasm
• Association with other type of carcinoma
• Often TTF-1 positive
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Non-Molar Gestational Trophoblastic Disease
• Choriocarcinoma
• Placental site trophoblastic tumor (PSTT)
• Epithelioid trophoblastic tumor
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Clinical Features ETT PSTT Choriocarcinoma
Clinical presentation
Vaginal bleeding Missed abortion Persistent GTD after hydatidiform mole
Last known pregnancy or GTD
Variable Variable Months
History of mole
14% 5-8% 50%
Serum hCG Low Low High
Treatment Hysterectomy Hysterectomy Chemotherapy
Modified from Blaustein’s Pathology of the Female Genital Tract, 5th edition
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Intermediate Trophoblastic Lesion LMWCK +
Implantation Site Intermediate Trophoblast
Chorionic type Intermediate Trophoblast
P63 + hPL-/+
P63 - hPL+++
EIS PSTT PSN ETT
Ki-67 <1% Ki-67 >10% Ki-67 <5% Cyclin E -
Ki-67 >15% Cyclin E ++
EIS: exaggerated implantation site PSTT: placental site trophoblastic tumor PSN: placental site nodule ETT: epithelioid trophoblastic tumor
Inhibin +
Low hCG
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B-hCG
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Ki-67
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Immunohistochemistry ETT Choriocarcinoma
P63 + +/- CK18 + +
Inhibin + +/-
hPL +/- +/-
Mel-CAM +/- +
hCG +/- +
Ki-67 10-25% >50%
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Choriocarcinoma
• Treated choriocarcinoma • Choriocarcinoma with areas predominantly
composed of intermediate trophoblasts
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Ki-67
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CASE 7
37F G1P1 (2 year old baby girl) Vaginal bleeding and bulky uterus on ultrasound Hysterectomy for “fibroids” Pre-op hCG = 27 000
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What is your diagnosis?
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INHIBIN
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HPL
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P63
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Ki-67
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What is your diagnosis?
How do you explain a beta-hCG of 27 000?
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Ki-67
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Immunohistochemistry ETT Choriocarcinoma
P63 + +/- CK18 + +
Inhibin + +/-
hPL +/- +/-
Mel-CAM +/- +
hCG +/- +
Ki-67 10-25% >50%
Clinical history and clinical presentation are important in distinguishing
ETT from Choriocarcinoma
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Reference • Buza N, Hui P (2014) Immunohisochemistry and other ancillary techniques in the diagnosis of gestrational
trophoblastic diseases. Semin Diagn Pathol 31: 223-232 • Kalhor N, Ramirez PT, Deavers MT, Malpica A, Silva EG (2009) Immunohistochemical studies of
trophoblastic tumors. Am J Surg Pathol 33: 633 – 638 • Kurman RJ Blaustein’s pathology of the female genital tract 5th edition. Springer-Verlag New York 2002. • Lewin SN, Aghajanian C, Moreira AL, Soslow RA (2009) Extrauterine epithelioid trophoblastic tumors
presenting as primary lung carcinomas. Am J Surg Pathol 33: 1809-1814 • Ronett BM, DeScipio C, Murphy KM et al (2014) Characteristics of hydatidiform moles: analysis of a
prospective series with p57 immunohistochemistry and molecular genotyping. Modern Pathol 27: 238-254.
• Ronett BM, DeScipio C, Murphy KM (2011) Hydatidiform moles: ancillary techniques to refine diagnosis. Int J Gynecol Pathol 30: 101-116.
• Shih IM, Kurman RJ (1998) Epithelioid trophoblastic tumor: a neoplasm distinct from choriocarcinoma and placental site trophoblastic tumor simulating carcinoma. Am J Surg Pathol 22: 1393-1403
• Shih IM, Kurman RJ (2004) P63 expression is useful in the distinction of epithelioid trophoblastic and placental site trophoblastic tumors by profiling trophoblastic subpopulations. Am J Surg Pathol 28: 1177 – 1183