Slide Presentation (SL-26): Pulmonary Pathology Jae Y. Ro, M.D., PhD Weill Medical School of Cornell University, Houston Methodist Hospital and UT MD Anderson Cancer Center, Houston, TX Cornell University October 17, 2018
Case: SMP18-xx405 81 year-old female with no past medical history No smoking history 1.1 cm RML mass was found on CT scan in Feb. 2016 when she came to “Emergency Room” for abdominal problems No symptoms related to mass, followed with CT scans and the mass had increased in size to 1.5 cm in April, 2017, and 1.7 cm in April, 2018
Case: SMP18-xx405 MRI brain was negative and no metastases found on PET scan CT-guided FNA in 4, 2018 positive for adenocarcinoma Under the clinical diagnosis of stage IA2 (T1b, N0, M0), robot-assisted videoscopic right middle lobectomy and mediastinal lymph node dissection
Feb. 2016
April 2017
April 2018
1 cm
SMP18-xx405 1.7 cm greatest dimension
SMP18- XX405 Diagnosis: Lung, RML, wedge resection: - Adenocarcinoma with micropapillary (40%), lepidic with papillary (40%) and acinar pattern (20%), 1.7 cm, high grade - Spread through alveolar space (STAS) - Pleura, free of tumor involvement - No LVI identified - Margins free of tumor - N1 and N2 LNs, free of tumor (0/13) Final TNM: pT1b pN0 cM0, stage IA2
Molecular Diagnostic Results (SMP18-xx405) CCDC6-RET gene rearrangement ALK gene rearrangement Not Detected ROS1 gene rearrangement Not Detected NTRK1 gene rearrangement Not Detected MET14 exon skipping Not Detected EGFR mutation Not Detected KRAS mutation Not Detected BRAF mutation Not Detected ERBB2/Her2 mutation Not Detected
Molecular Diagnostic Results (SMP18-xx405) PD-L1 negative in tumor and immune cells CCDC6-RET gene rearrangement acquired resistance to EGFR directed treatment is the development of the T790M mutation in exon 20 of EGFR another mechanism of acquired EGFR resistance
Micropapillary component in lung adenocarcinoma (MPC): a distinctive histologic features with possible prognostic significance Am J Surg Pathol 2002 Mar;26 (3): 358-64 Amin MB, Tamboli P, Merchant SH, Ordonez NG, Ro J, Ayala AG and Ro JY Department of Pathology, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA
Micropapillary carcinoma (MPC) Reported 35 cases, MDACC experience Of 35 cases, 15 cases available for blocks CK7+ (14/15), CK20+ (2/15), TTF1 (12/15) 33 of 35 metastasis: LN (n=26), lung (n=17), brain and bone (n=9, each), and other sites F/U on 29 (mean F/U months, 25): 16 of 29 patients (55%) AWD, 5 (17%) DOD, and 8 (28%) AWOD MPC, possible primary in lung in addition to breast, urinary bladder, and ovary Am J Surg Pathol 2002 Mar;26 (3): 358-64
2004 WHO Classification of Adenocarcinoma Adenoca, mixed subtype: majority (80-85%) Acinar adenocarcinoma Papillary adenocarcinoma Bronchioloalveolar carcinoma –Non-mucinous, –Mucinous, –Mixed Solid adenoca with mucin production Fetal adenocarcinoma Mucinous “colloid” carcinoma Mucinous cystadenocarcinoma Signet ring adenocarcinoma Clear cell adenocarcinoma
MPC of lung In 2002 Drs. Ro and Ayala with fellows Unique pathologic, clinical and molecular features Aggressive clinical course EGFR TKI therapy: Targeted therapy: cornerstone for new lung tumor classification (IALCS/ATS/ERS)
Proposed IASLC/ATS/ERS Adenocarcinoma classification (2011) Preinvasive lesions •Atypical adenomatous hyperplasia •Adenoca in situ (BAC): non-mucinous Minimally invasive adenoca (lepidic predominant tumor with ≤5 mm invasion) Invasive adenocarcinoma • Lepidic predominant (non-mucinous BAC) • Acinar predominant • Papillary predominant • Micropapillary predominant • Solid predominant • Variants: Mucinous adenoca (mucinous BAC), Colloid, Fetal (low, high grade), and Enteric
2015 WHO Classification of Adenocarcinoma Lepidic adenocarcinoma Acinar adenocarcinoma Papillary adenocarcinoma Micropapillary adenocarcinoms Solid adenocarcinoma Invasive mucinous adenocarcinoma Mixed invasive mucinous and non-mucinous Colloid adenocarcinoma Fetal adenocarcinoma Enteric adenocarcinoma Minimally invasive adenocarcinoma Non-mucinous Mucinous Preinvasive lesions: AAH and adenoca in situ
MP
Papillary and MP
Micropapillary carcinoma in WHO 2015 Papillary tufts forming florets that lacks fibrovascular cores These may appear detached from and/or connected to alveolar walls Tumor cells are usually small and cuboidal with variable nuclear atypia Ring-like glandular structures may floats within alveolar spaces Vascular and stromal invasion common Psammoma bodies may be seen
Lepidic
Lepidic with microinvasion
Acinar
Solid with mucin
True Papillary Carcinoma of the Lung: A Distinct Clinicopathologic Entity Silver and Askin. Am J Surg Pathol 1997;21:43-51
Am J Surg Pathol 1997;21:43-51
Miyoshi et al: Am J Surg Pathol 27:101–9, 2003
1. Multiple tight clusters in spaces 2. Thin slender nests, < 4 cell thick 3. Nuclei, inverted polarity
MPC in lung adenocarcinoma, 2002 Micropapillary carcinoma component has been reported in other organs to have worse prognostic significance: Breast Urinary bladder Ovary 2004 WHO classification of lung tumors, four major types and five variants of adenocarcinoma (histologic growth patterns) No reference to micropapillary histology Amin, Tamboli, Merchant, Ordonez, Ro, Ayala and Ro. Am J Surg Pathol. 2002; 26(3): 358–364
MPC in lung adenocarcinoma, 2002 Size of primary tumors: 0.8 to 6.0 cm Tumors Well circumscribed Gray-white/tan-yellow cut surface Focal areas of hemorrhage and necrosis Mixture of various histologic subtypes (acinar, papillary, solid, BA) Amount of micropapillary component varied 21%, focal (<5%); 58%, moderate (5-30%); 21%, extensive (>30%) Amin, Tamboli, Merchant, Ordonez, Ro, Ayala and Ro. Am J Surg Pathol. 2002; 26(3): 358–364
MPC in lung adenocarcinoma, 2002 & 2004 74% had metastasis at initial presentation (additional ones at follow up) 81% lymph node metastasis (additional ones to extra-mediastinal LN) 53% intrapulmonary metastasis Follow up Other sites of metastasis 4-144 Brain, bone, liver, jejunum months Adrenal gland, skin Amin, Tamboli, Merchant, Ordonez, Ro, Ayala and Ro. Am J Surg Pathol. 2002; 26(3): 358–364 Nassar. Adv Anat Pathol. 2004;11(6):297-303
MPC: A distinct pathological marker of poor prognosis, 2005 Study 122 cases of small lung adenocarcinoma, 55% MPP positive vs. 45% negative MMP (+) MMP (-) Lymph node metastasis 74% 26% Pleural invasion 55% 34% 5 year survival 54% 81% Makimoto, et al. Histopathology. 2005; 46(6):677-84
MPC: A distinct pathological marker of poor prognosis, 2005 Makimoto, et al. Histopathology. 2005; 46(6):677-84
MPC: A distinct pathological marker of poor prognosis, 2005 Summary: Significant association with MP and - LN metastasis - Pleural invasion - Stage MP distinct pathological marker Presence crucial, size and amount NOT Makimoto, et al. Histopathology. 2005; 46(6):677-84
Histopathological features and prognostic significance of MPC in lung adenoCA, 2008 Clinicopathologic factors • Prognostic significance Significantly associated with MP Smoking LN metastasis Pleural invasion Lymphatic invasion Venous invasion Dominant BAC subtype Dominant papillary subtype No association with age, gender or tumor size Kamiya, et al. Mod Pathol. 2008; 21(8):992-1001
Histopathological features and prognostic significance of MPC in lung adenoca, 2008 Kamiya, et al. Mod Pathol. 2008; 21(8):992-1001
Prognostic factors of survival after recurrence in patients with resected lung adenocarcinoma, 2015 Clinicopathologic characteristics of 179 patients with recurrence after complete resection of lung adenocarcinoma Hung, et al. J Thorac Oncol. 2015
Micropapillary Carcinoma of lung The more the MP in stage I lung adenoca, the worse the prognosis—a retrospective study on digitalized slides: Virchows Arch. 2018 Jun;472(6):949-958. Presence of MP and solid patterns are associated with nodal upstaging and unfavorable prognosis among patients with cT1N0M0 lung adenocarcinoma: a large-scale analysis: J Cancer Res Clin Oncol. 2018 Apr;144(4):743-749. Prognostic significance of the IASLC/ATS/ERS (WHO 2015) classification of stage I lung adenocarcinoma: A retrospective study based on analysis of 110 Chinese patients. Thorac Cancer. 2017 Nov;8(6):565-571.
A Grading System of Lung Adenoca Based on Histologic Pattern is Predictive of Disease Recurrence in Stage I Tumors Am J Surg Pathol 2010;34:1155–1162 Lepidic (BAC) Acinar, papillary Solid, micropapillary
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