5/25/2013 Case 1 Illuminating Consultation • 44 year old woman with a mass in the Cases rectus muscle. • Biopsy performed, reviewed at UCSF. • Immunostains evaluated: Charles Zaloudek, M.D. – Positive: Pankeratin, keratin AE1/AE3, CK7 – Negative: CK20, TTF-1, ER, CD34, CD31, Department of Pathology S100, INI1 (positive stain, negative result) University of California • Diagnosis: Carcinoma, likely metastatic, San Francisco pancreaticobiliary, gyn, skin adnexal Case 1 (Contributed by Rebecca Swain MD) • 9 cm tan-yellow whorled mass • Located in rectus abdominis muscle • Deep to a C-section scar from 20 years ago • Did not grossly involve the peritoneum • Excised 1
5/25/2013 Tumors and Masses of the Abdominal Wall (From Current Diagnosis and Treatment: Surgery) • Hernia • Lipoma • Hemangioma • Endometriosis • Fibromatosis (desmoid tumor) • Malignant tumor – most are metastatic, lung and pancreas are the most common primary sites 2
5/25/2013 Immunohistochemistry of Summary Trophoblastic Tumors General trophoblastic markers: HSD3B1, • Young woman CD10, inhibin, CK18, pankeratin • Tumor in the anterior abdominal wall • Pan keratin and CK7 positive Best Marker MIB1 Rate • No internal primary site identified Choriocarcinoma hCG +++ • Related to a C-section scar ETT p63 + or ++ PSTT hPL + or ++ • PO Day 1 serum hCG = 27 IU/L, PO Day 3 serum hCG = 9 IU/L HCG HPL Inhibin Case 1 Another Case p63 3
5/25/2013 Ki-67 Diagnosis Epithelioid Trophoblastic Tumor Epithelioid Trophoblastic Tumor Description of 14 Cases of A New Type of Trophoblastic Tumor • Patient age 15-66 (average 36) • Antecedent pregnancy: • Shih IM and Kurman RJ. Epithelioid – Normal delivery 68% – Spontaneous abortion 16% trophoblastic tumor – A neoplasm – Hydatidiform mole 16% distinct from choriocarcinoma and • Interval 1-25y (average 6.2) placental site trophoblastic tumor • Presentation: amenorrhea or abnormal simulating carcinoma. Am J Surg bleeding – can be misdiagnosed as ectopic • Some patients present with extrauterine Pathol, 1998; 22:1393-1403. tumors – lung or other sites • Low levels of HCG 4
5/25/2013 p63 Epithelioid Trophoblastic Tumor • DNA genotyping reveals paternal alleles that are not present in adjacent maternal tissues � trophoblastic hPL origin • Conflicting data on Y-chromosome, but a recent study suggested that most ETT do not have Y chromosome material present (paternal X favored) Chorionic IT – Chorion Laeve Epithelioid ETT Cervix T rophoblastic Location of Primary Tumor T umor • Cervix or LUS 50% • Corpus 30% • Extrauterine 20% • Moral: Can be easily mistaken for cervical cancer 5
5/25/2013 Coulson, L. E., et al. (2000). "Epithelioid trophoblastic tumor of the uterus in a postmenopausal woman - A case report and review of the literature." American Journal of Surgical Pathology 24 (1 1): 1558-1562. 6
5/25/2013 ETT - CK18 HPL HCG ETT Immunohistochemistry : - Scattered HPL, HCG, PLAP , Mel-CAM + cells. - p63+, HLA-G+ - MIB1 10-25% ETT One of the original descriptions Mazur MT. Metastatic gestational choriocarcinoma. Unusual pathologic variant following chemotherapy. Cancer. 1989; 63:1370-1377. Two lung tumors reported. 7
5/25/2013 p63 ETT in the Lung CK18 Epithelioid Trophoblastic Tumor • Clinical behavior similar to PSTT • Most have benign clinical evolution • ~25% metastasize • Serum HCG, although low, can be used to monitor treatment • May not respond to standard GTD chemotherapy • Hysterectomy is standard therapy • Resection of metastases may help Gestational Trophoblastic Case 1 Key Points Neoplasia • ETT is derived from intermediate trophoblasts of the • Persistent or invasive hydatidiform chorion laeve • Low levels of serum HCG mole • Usually primary in the cervix or uterus • Choriocarcinoma • Nodular, epithelioid appearance resembles a carcinoma • Differential diagnosis • Epithelioid Trophoblastic Tumor (ETT) – Squamous cell carcinoma of the cervix: CK5/6, p16, HPV testing; LMW CK, staining for trophoblastic markers, • Placental Site Trophoblastic Tumor molecular genotyping – Placental site nodule: size, cellularity, low MI, low Ki-67 (PSTT) • Difficult to treat with chemotherapy, hysterectomy is usually performed • Mixed Trophoblastic Tumor • Extrauterine primary tumors occur in the lungs, pelvis and elsewhere 8
5/25/2013 Case 2 (Contributed by Dave Park) • 41 year old G5P3 • Persistently elevated HCG in the range of 200-300 IU/L • Underwent a D&C for suspected missed abortion. 9
5/25/2013 hCG hPL Desmin p63 Immunohistochemistry of Summary Trophoblastic Tumors General trophoblastic markers: HSD3B1, • Intrauterine CD10, inhibin, CK18, pankeratin • Ill defined, invades the myometrium • Polygonal cells, atypia, mitotic Best Marker MIB1 Rate activity Choriocarcinoma hCG +++ • Low HCG and p63, extensive HPL ETT p63 + or ++ PSTT hPL + or ++ • Diagnosis: Placental site trophoblastic tumor (PSTT) 10
5/25/2013 1. Twiggs LB, Okagaki T, Phillips GL, Stroemer JR, Adcock LL. Trophoblastic pseudotumor-evidence of malignant disease potential. Gynecologic Oncology 1981;12:238-48. Trophoblastic Pseudotumor of the Uterus 2. Gloor E, Dialdas J, Hurlimann J, Ribolzi J, Barrelet L. Placental site trophoblastic tumor (trophoblastic An exaggerated form of “Syncytial pseudotumor) of the uterus with metastases and fatal Endometritis” Simulating a Malignant outcome. Clinical and autopsy observations of a case. American Journal of Surgical Pathology 1983;7:483-6. Tumor 3. Eckstein RP, Russell P, Friedlander ML, Tattersall MH, Robert J Kurman, MD (MAJ, Bradfield A. Metastasizing placental site trophoblastic MC, USA), Robert E Scully, MD, tumor: a case study. Human Pathology 1985;16:632-6. and Henry J Norris, MD Scully RE, Y oung RH. T rophoblastic pseudotumor: A reappraisal. Am J Surg Pathol 1981; 5:75-76. Cancer 38:1214-1226, 1976 Proposed name Placental Site T rophoblastic T umor PSTT at NETDC Placental Site Trophoblastic Tumor (Gynecol Oncol 82:415-419, 2001) PSTT • 13 patients, average age lower 30’s • Mean age about 31y, range 20 to 63y • Most antecedent pregnancies normal or • 60-70% follow an uneventful term pregnancy, abortion; hydatiform mole rare the rest follow CHM or abortion • Average time from antecedent pregnancy to • Requirement for a paternal X chromosome; diagnosis ~16m (2w - 5y) antecedent gestation female • Time from previous pregnancy to PSTT • Serum hCG slightly elevated (< 500 diagnosis 1 week to 204m, median 12-18m mIU/ml) • Presentation is with vaginal bleeding, uterine • Treatment usually by hysterectomy; 4 had enlargement pelvic metastases at diagnosis • Usually slight to moderate elevation of serum • 43% had recurrences; all had received hCG chemotherapy • About 85% of cases are in stage I at diagnosis 11
5/25/2013 Placental Site T rophoblastic T umor – Gross Appearance A tumor mass is almost always present Ill defined edge, not sharply circumscribed 12
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5/25/2013 PSTT Immunohistochemistry • Positive – Cytokeratin cocktail – LMW cytokeratin (CK18) – Inhibin – hPL (97% +, 56% strong +) – CD146 (MelCAM), HLA-G • Negative or weak – hCG (almost always scattered + cells) – PLAP, p63 PSTT - CK18 PSTT - MIB1 HPL HCG 14
5/25/2013 Differential Diagnosis Differential Diagnosis • Exaggerated placental site reaction • Squamous cell carcinoma : Different – A benign expansion of the normal population of appearance, different immunophenotype implantation site intermediate trophoblasts in the placental bed • Choriocarcinoma : Different cell – High cellularity can mimic PSTT – No mass in EPS Reaction population, less proliferation, different – Can be very cellular, but lacks cohesive masses of HCG profile, different immunophenotype cells – Does not permeate and splay the myometrium • ETT : Related, but different cytology, – Minimal mitotic activity and Ki-67 immunoreactivity different low power appearance, – Lack of a genetic association with PSTT – majority have a paternal Y chromosome different immunophenotype EPS CK hPL Ki-67 Exaggerated Placental Site Reaction 15
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