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Endometrial Polyp • Polypoid Adenomyoma • Other Benign Glands + Malignant Stroma

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The Hawaii Pathology Conference: The Mighty Women of Pathology Mixed Müllerian Tumors: Does Adenofibroma Exist? Do You Grade Adenosarcoma? If So, How? Are All Carcinosarcomas Equal? Teri A Longacre, MD, Richard L Kempson Endowed Professor of Surgical Pathology, Department of Pathology, Stanford Medicine Notice of Faculty Disclosure US Pathology Biomarker Advisory Board, Merck Teri Ann Longacre, MD Introduction • Polypoid adenomyoma - Atypical polypoid adenomyoma • Adenofibroma – Adenosarcoma • Carcinosarcoma Benign Glands + Benign Stroma • Polypoid Adenomyoma (PA) • Atypical Polypoid Adenomyoma (APA) • Atypical Polypoid Adenomyoma of Low Malignant Potential (APA-LMP) • Adenofibroma • Other (benign) polyps Case 1 • 32 year old with cervical polyp Is it? • Adenofibroma • Adenosarcoma • Atypical polypoid adenomyoma • Other Polypoid Adenomyoma (PA) • Age range from 26 to 64 (median, 47 years) • Abnormal vaginal bleeding • Size 0.3 to 17 cm • Corpus, most submucosal (80%) • Cervix uncommon (10%) • Firm, cystic polypoid masses Int J Gynecol Pathol 2000;19:195-205 Polypoid Adenomyoma (PA) • Circumscribed • Fibromuscular tissue – endometrial stroma often present around glands • Simple, rounded or tubular shaped glands & cysts – no atypia! • Focal tubal metaplasia • Squamous (morules) metaplasia rare, but may be present Int J Gynecol Pathol 2000;19:195-205 Desmin CD10 Polypoid Adenomyoma (PA) • Uncommon • Probably related to adenomyosis • No clear association with infertility • No risk of recurrence Int J Gynecol Pathol 2000;19:195-205 Summary: Polypoid Adenomyoma • Uncommon • No gland architectural abnormalities • Squamous metaplasia rare • No risk of recurrence • Important to distinguish from atypical polypoid adenomyoma Case 2 • 38 year old with cervical polyp APA APA Is it? • Complex endometrial hyperplasia • Adenosarcoma • Low-grade endometrial adenocarcinoma • Polypoid adenomyoma • Other Atypical Polypoid Adenomyoma (APA) • Circumscribed • Fibromuscular tissue – endometrial stroma may be present • Crowded, architecturally complex glands with atypia • Squamous (morular) metaplasia (90%) • Stromal mitotic figures may be focally increased MICRO: Morules Atypical Polypoid Adenomyoma (APA) • Reproductive age (mean, 38 years) • Vaginal bleeding or infertility work-up • Lower uterine segment polyp – can be removed by curettage Atypical Polypoid Adenomyoma (APA) • Mimics myoinvasive endometrial carcinoma in curettings • Look for dimorphic pattern: APA + normal proliferative or secretory endometrium • Immunostains for SMA, desmin not useful! • CD10 (so-called fringe pattern) expression in myoinvasive cancer but not APA may be useful Hum Pathol 2008;39:1446-53. Atypical Polypoid Adenomyoma (APA) • Atypical polypoid adenomyoma has risk of recurrence, but can be treated by polypectomy in reproductive-age women • Rarely atypical polypoid adenomyoma develop into low grade adenocarcinoma & very rarely spread beyond uterus Am J Surg Pathol 1996;20:1-20 Atypical Polypoid Adenomyoma of Low Malignant Potential • Looks like low grade cancer, invades like low grade cancer… • So, probably is very low grade cancer • But to date, deep myometrial invasion very uncommon and very rare instances of extension beyond uterus, so clinical behavior is that of a low malignant potential tumor Atypical Polypoid Adenomyoma of Low Malignant Potential • More architecturally complex than APA Higher rate of recurrence than APA: 60% versus 33% • Higher rate of progression to carcinoma than APA: up to 20% may have superficial myoinvasion Am J Surg Pathol 1996;20:1-20 Summary: Atypical Polypoid Adenomyoma • Gland architectural abnormalities • Squamous metaplasia common • Risk of recurrence 33-60% • Can be managed conservatively • Important to distinguish from endometrioid adenocarcinoma Case 3 • 42 year old with vaginal bleeding Is it? • Complex endometrial hyperplasia • Adenosarcoma • Low-grade endometrial adenocarcinoma • Polypoid adenomyoma • Other Well Differentiated Endometrioid Adenocarcinoma • Myoinvasive adenocarcinoma in endometrial sampling is very uncommon • When present, glands are haphazardly set in myofibromatous stroma with stromal reaction • Evidence of adenocarcinoma often present elsewhere in sampling: glands typically more complex with more cytologic atypia Case 4 • 44 year old with vaginal bleeding Is it? • Complex endometrial hyperplasia • Adenosarcoma • Low-grade endometrial adenocarcinoma • Polypoid adenomyoma • Other Focal Polypoid (Nodular) Hyperplasia • Similar presentation as APA/APA-LMP • Dimorphic pattern • Can probably be managed as APA Case 5 • 44 year old with vaginal bleeding Is it? • Adenofibroma • Adenosarcoma • Benign endometrial polyp • Polypoid adenomyoma • Other Benign Glands + Malignant Stroma • Low-grade adenosarcoma Mesodermal Adenosarcoma • Uncommon • Biphasic neoplasm composed of benign glands and sarcomatous stroma • Corpus > Ovary > Cervix • Peritoneal and extra-genital sites • Rare in testis, seminal vesicle, prostate Mesodermal Adenosarcoma • Assoc. w/ endometriosis, esp extragenital sites • Unopposed estrogen, tamoxifen, radiation • Slow growing, recurrences at 5 or more years (sometimes >10 years) • Clinical behavior depends on: – site – stromal overgrowth – heterologous elements and/or high grade sarcomatous element Adenofibroma/Adenosarcoma Spectrum AdenoFib AdenoSarc Uterine Adenosarcoma • Postmenopausal, may occur in reproductive years • Polyp or polypoid lesion protruding through cervical os (1-17 cm; mean, 5 cm) • Vaginal bleeding • Often history of “recurrent polyps” Cancer 1981;48:354-366; Hum Pathol 1990;21:363-368 Cervical Adenosarcoma • Younger women, 13–67 years (mean, 38) • Vaginal bleeding • Initially interpreted as “benign cervical polyps” • Often smaller than their uterine counterparts (2–8 cm) • Arise in ecto- or endocervix, most low stage Ovarian Adenosarcoma • Reproductive & postmenopausal (50% less than 50 years) • Unilateral • Solid & cystic, 5.5-50 cm (mean, 14 cm) • +/- assoc. w/ endometriosis • Poor prognosis compared to uterine/cervix adenosarcoma Am J Surg Pathol 2002;26:1243-1258 Peritoneal Adenosarcoma • Mean age 41 years, but wide range • History of prior hysterectomy many years prior to presentation: Metastasis from unrecognized uterine primary or true de novo? • Assoc w/ endometriosis • Bladder, colorectum, omentum, recto- vaginal septum, pouch of Douglas, retroperitoneum Adenosarcoma by Location Recurrences Deaths Corpus 15-25% 10-25% (45-70%**) (54%**) Cervix 18% 12% Ovary 77% 64% Peritoneum 60% 40% ** Stromal overgrowth Do You Grade Adenosarcoma? • Actually…you do Adenosarcoma: 3 Groups • Group 1: Usual (low-grade) adenosarcoma (Exclude benign tumor) • Group 2: Adenosarcoma with high grade sarcoma (R/O other sarcoma) • Group 3: Adenosarcoma with stromal overgrowth (SO), defined as pure sarcoma comprising >25% of tumor volume – usually high-grade, often heterologous (rhabdomyosarcoma) Adenosarcoma: Usual • Uniform distribution of irregular, often cystic glands with polypoid intrusions (phyllodes-like) • Variably cellular stroma with accentuation or condensation around glands (cambium layer) • Stromal cytologic atypia (usually mild) • Stromal mitotic figures: threshold varies from 2* to 4** MF/ 10 HPF * Clement & Scully, 1990; ** Zaloudek & Norris, 1981 MMMT Adenosarcoma Endometrioid Squamous Ciliated (Eosinophilic) Mucinous Nondescript Decidualized Sex cord elements Smooth muscle Adenosarcoma with High Grade Sarcomatous Stroma • High-grade sarcoma present but no stromal overgrowth – usually with heterologous elements • Rhabdomyosarcoma • Chondrosarcoma • Osteosarcoma Adenosarcoma with Stromal Overgrowth (SO) • Defined as pure sarcoma comprising >25% of tumor volume • Usually high-grade sarcoma, often heterologous • Rarely, low-grade sarcoma (slightly improved prognosis?) Adenosarcoma: Treatment • Surgical excision is mainstay • Radiation, chemotherapy or both for metastatic disease • Hormonal therapy for low stage disease – the stromal component frequently expresses hormone receptors Adenosarcoma: Differential Diagnosis • Adenofibroma • Endometrial polyp • Polypoid endometriosis • Carcinosarcoma Summary: Adenosarcoma • Biphasic benign epithelial and malignant stromal proliferation • Low-grade delayed, local recurrence vs high-grade sarcomatous overgrowth rapid recurrence with metastatic potential • Behavior depends also on site of origin Case 6 • 54 year old with vaginal bleeding Is it? • Adenofibroma • Adenosarcoma • Benign endometrial polyp • Polypoid adenomyoma • Other Benign Glands + Benign Stroma • Adenofibroma Adenofibroma - Adenosarcoma • Paucicellular, fibromatous • Uniform distribution of or fibrotic stroma irregular, often cystic • Stroma is mitotically glands with polypoid active intrusions • Multiple epithelial • Periglandular stromal differentiated types: condensation is minimal endometrioid, squamous, or absent mucinous, etc • Polypectomy is adequate • Variably cellular stroma treatment, provided that’s with accentuation or all there is condensation around • If in doubt, imaging, re- glands (cambium layer) sampling, close f/u • Hysterectomy is treatment of choice Does Adenofibroma Exist? • Controversial • Spectrum problem • May not be single entity Adenofibroma Is Genetically Heterogeneous • MDM2 amplification 26-28% • MYBL1 (sarcomatous overgrowth) 22% • PIK3CA/AKT/PTEN pathway 72% • ATRX (sarcomatous overgrowth) 17% • Chromosomal instability in aggressive tumors J Pathol 2015;235:37-49; J Pathol 2016;238:381-8; Mod Pathol 2016; 29:1070-82 Case 7 • 54 year old with vaginal
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