5/22/2014 Outline of Talk Endocervical Adenocarcinoma Treatment - PowerPoint PPT Presentation

5/22/2014 Outline of Talk Endocervical Adenocarcinoma � Treatment Decisions for Endocervical Adenocarcinoma Challenges in Classification, Differential Diagnosis and Reporting � New 2014 WHO Classification system � Update on Mucinous Adenocarcinoma variants � Common Problems in Usual type Endocervical Adenocarcinoma Joseph Rabban MD MPH Pathology Department General Treatment Decisions for Adenocarcinoma of Cervix General Treatment Decisions for Adenocarcinoma of Cervix UCSF Division of Gynecologic Oncology, 2014 UCSF Division of Gynecologic Oncology, 2014 � If specimen is a cone : � If specimen is a biopsy and tumor is not clinically visible: Key Factors Cone procedure, regardless of AIS, early or deep invasion � Desire for fertility preservation � In situ versus invasive adenocarcinoma � If specimen is a biopsy and tumor is clinically visible: � Early versus >Early stromal invasion Depth, horizontal spread Hysterectomy / radiation � Lymphovascular invasion � Margin status Less Critical Factors � Histologic subtype of adenocarcinoma � Tumor grade 1

5/22/2014 General Treatment Decisions for Adenocarcinoma of Cervix General Treatment Decisions for Adenocarcinoma of Cervix UCSF Division of Gynecologic Oncology, 2014 What is the definition of “early invasive” adenocarcinoma ? � If specimen is a cone : Different definitions exist: Invasion Margins LVI Fertility Treatment None Negative No Yes Observation, repeat Pap/ECC FIGO/AJCC IA1, pT1a1 Depth <3 mm and spread <7 mm Positive No Yes Repeat cone IA2, pT1a2 Depth 3 to 5 mm and spread <7 mm Negative No No Hysterectomy Early Negative No Yes Observation, repeat Pap/ECC SGO microinvasion Depth <3 mm and NO LVI >Early Negative No Yes Trachelectomy >Early Negative Yes Yes Radical trachelectomy / nodes >Early No Radical hysterectomy/nodes versus XRT Positive margins preclude definitive diagnosis of “early” invasion General Treatment Decisions for Adenocarcinoma of Cervix Positive Margins Preclude Classifying as Early Invasion UCSF Pathology Report Template � Invasive tumor type � Invasive tumor grade � Depth of invasion (mm) � Horizontal spread of invasion (mm) � LVI � Margin for invasive tumor � Margin for in situ tumor � Margin for HSIL 2

5/22/2014 3 rd Edition: 2003 4 th Edition: 2014 Outline of Talk � Treatment Decisions for Endocervical Adenocarcinoma � New 2014 WHO Classification system � Update on Mucinous Adenocarcinoma variants � Common Problems in Usual type Endocervical Adenocarcinoma 3 rd Edition: 2003 4 th Edition: 2014 3 rd Edition: 2003 4 th Edition: 2014 What has changed ? Evolving understanding of “Mucinous” adenocarcinoma types Eliminated as a distinct tumor “type” � Glandular dysplasia � Not commonly associated with high risk HPV � Early invasive adenocarcinoma (a tumor stage , not a type ) � Often cytologically bland � No adenocarcinoma in situ of usual type Elevated to a distinct tumor “type” � Uncertain precursor lesion (? Atypical LEGH) � Villoglandular type � Often p16 negative / patchy � Usual type � Worse prognosis � Risk for Peutz Jeghers syndrome Re-classified within a larger “type” � Minimal deviation type = form of gastric type mucinous adenocarcinoma 3

5/22/2014 3 rd Edition: 2003 4 th Edition: 2014 2014 WHO Classification of Adenocarcinoma of Cervix � Endocervical adenocarcinoma in situ, usual type Evolving understanding of “Mucinous” adenocarcinoma types � Endocervical adenocarcinoma, usual type � Mucinous carcinoma Screening Challenges NOS type � High risk HPV testing may not be effective Gastric type (including minimal deviation type) � Precursors may be difficult to recognize in Pap test Intestinal type Signet ring cell type Diagnostic Challenges � Villoglandular carcinoma � Difficult to distinguish from benign proliferations � Difficult to distinguish from metastasis of primary GI tumors � Endometrioid carcinoma Treatment Challenges � Clear cell carcinoma � Should more aggressive or different options be considered � Serous carcinoma � Mesonephric carcinoma Genetic Counseling � Adenocarcinoma admixed with neuroendocrine carcinoma � Which patients to evaluate for risk for Peutz Jeghers syndrome ? Prevention Challenges � HPV vaccination may not be effective for these types 2014 WHO Classification of Adenocarcinoma of Cervix 2014 WHO Classification of Adenocarcinoma of Cervix Tumor Grading Tumor Staging � WHO does not provide specific criteria � WHO advocates FIGO / AJCC staging criteria � FIGO / AJCC does not provide specific criteria � New 2014 edition of FIGO staging: NO changes Mentions option of well / moderate / poorly differentiated � Practical approach: 1. Apply FIGO criteria of endometrial adenocarcinoma 2. Certain histologies are tied to grade: � Villoglandular type = well differentiated � Minimal deviation type = well differentiated � Serous carcinoma = high grade 4

5/22/2014 2014 WHO Classification of Adenocarcinoma of Cervix Outline of Talk Prognosis � Treatment Decisions for Endocervical Adenocarcinoma � Mostly dependent on FIGO stage � New 2014 WHO Classification system Stage 5 y survival IA1 100 % IA2 93 % � Update on Mucinous Adenocarcinoma variants IB1 89 % IB2 83 % II 49 % � Common Problems in Usual type Endocervical Adenocarcinoma III 34 % IV 3 % � Worse than Usual type Adenocarcinoma Gastric type Adenocarcinoma with neuroendocrine carcinoma Serous carcinoma � Better than Usual type Adenocarcinoma Villoglandular type What is the meant by “mucinous” ? Normal Endocervix Usual Type Adenocarcinoma Morphology Mucins H&E Stains Normal acid mucin blue-grey endocervix neutral mucin Usual type mucin depleted minimal Adenocarcinoma eosinophilic Gastric type neutral mucin clear / pale MUC6 Adenocarcinoma (pyloric mucin) eosinophilic HIK1083 Intestinal type intestinal goblet cells CDX2 Adenocarcinoma mucin 5

5/22/2014 Intestinal Differentiation Gastric differentiation / Pyloric metaplasia CDX2 Pyloric Glands of Stomach Pyloric Mucin: HIK1083, MUC6 Courtesy Kay Park MD Mucinous Adenocarcinomas of the Cervix Gastric type Adenocarcinoma of Cervix Definition: � Mucinous carcinoma, gastric type � Tumor cells with abundant clear to eosinophilic cytoplasm Minimal deviation type � Distinct cell membranes Gastric type � Pyloric gland mucin markers (MUC6, HIK1083) � Mucinous carcinoma, intestinal type � Well-differentiated = Minimal deviation type (“adenoma malignum”) � Mucinous carcinoma, signet ring cell type � All other grades = Gastric type Epidemiology: � In Japan, this is up to 25% of cervical adenocarcinomas � Usually not associated with high risk HPV � Some patients have Peutz Jeghers syndrome ( STK11 mutation) � Worse prognosis than usual type adenocarcinoma 6

5/22/2014 Gastric type Mucinous Adenocarcinoma of Cervix Gastric type Adenocarcinoma of Cervix Microscopic features: � Simple glands that are irregularly dilated � Haphazard growth in stroma � Minimal to no desmoplastic stroma � Abundant clear to eosinophilic cytoplasm � Distinct cell membranes Immunohistochemistry: � P16: often negative or patchy positive � CK7: positive � CK20: negative or focal positive � p53: can be positive � ER: negative. Courtesy Kay Park MD Gastric type Mucinous Adenocarcinoma of Cervix Gastric type Mucinous Adenocarcinoma of Cervix Courtesy of Glenn McCluggage MD Courtesy of Glenn McCluggage MD 7

5/22/2014 Gastric type Mucinous Adenocarcinoma of Cervix Minimal Deviation Type Adenocarcinoma of Cervix Courtesy Kay Park MD Minimal Deviation Type Adenocarcinoma of Cervix Minimal Deviation Type Adenocarcinoma of Cervix Mostly well differentiated Focal atypia 8

5/22/2014 Minimal Deviation Type Adenocarcinoma of Cervix Gastric type Adenocarcinoma of Cervix Oddly angled simple glands Focal desmoplastic stroma Precursor lesion: � Not usual type AIS � ? Atypical Lobular Endocervical Glandular Hyperplasia (LEGH) LEGH � Rare, benign proliferation of endocervical glands with gastric differentiation � Asymptomatic incidental finding or watery discharge 3 rd to 7 th decade � � Gross: circumscribed collection of cysts near the os � Well demarcated proliferation of glands centered around a central duct. � Abundant clear to eosinophilic cytoplasm � Bland nuclei Lobular Endocervical Glandular Hyperplasia Lobular Endocervical Glandular Hyperplasia Courtesy of Glenn McCluggage MD Courtesy of Glenn McCluggage MD 9

5/22/2014 Lobular Endocervical Glandular Hyperplasia Lobular Endocervical Glandular Hyperplasia Courtesy of Glenn McCluggage MD Courtesy of Glenn McCluggage MD Lobular Endocervical Glandular Hyperplasia Lobular Endocervical Glandular Hyperplasia HIK1083 Courtesy Kay Park MD Courtesy Kay Park MD 10