Case 4 Junya Fukuoka, MD. PhD. Nagasaki University Graduate School - PowerPoint PPT Presentation

Case 4 Junya Fukuoka, MD. PhD. Nagasaki University Graduate School of Biomedical Sciences Kameda Medical Center

Case 4: Pulmonary nodule • 50 year old woman detected to have abnormal shadow in her regular health screening. • Never smoking history. • No familial history of lung disease. • Left upper lobe mass. • Lobectomy was performed.

Pathological features by H&E • Single nodule with abundant mucin production • Focal papillary structure • Focal inflammatory changes • Focal ciliated epithelia • Minimal cellular atypia • No mitosis • Multi‐focal basal cell hyperplasia

Differential diagnosis (H&E): • Early invasive mucinous adenocarcinoma (IMA) • Inflammatory scar with abundant bronchiolar metaplasia • Glandular papilloma • Mixed squamous and glandular papilloma • Ciliated muconodular papillary tumor (CMPT) • Metastatic carcinoma from GI tract (esp panc)

HNF4α TTF‐1 CK7 p40

BRAF (V600E)

Differential diagnosis: • Early invasive mucinous adenocarcinoma (IMA) • Inflammatory scar with abundant bronchiolar metaplasia • Glandular papilloma • Mixed squamous and glandular papilloma • Ciliated muconodular papillary tumor (CMPT)

Ciliated muconodular papillary tumor (CMPT) • Recently proposed disease. • First report is 2002 (Japanese) by Ishikawa et al. • Nearly 40 cases reported, mostly from Asia. • Harboring frequent mutation • No recurrent occur but does not have long term follow up data • Little association with bronchial wall • Female ≒ male • Little association with smoking • Solitary nodule (1‐2cm) >> multiple

Molecular data of CMPT • BRAF V600E • KRAS G12D, G12V, G12C • EGFR ex19/20 uncommon mut • HRAS , ALK mutation (very few)

IHC of CMPT • TTF1 mostly+ • CK7+ / CK20‐ (may be focal+) • HNF4α (vary ++, +, ‐) • p40, p63+ basal cells (continuous or discontinuous) • p53 mostly wild type pattern.

Then, how about this case? • 71 year old woman • Detected to have abnormal shadow. • No symptom • Never smoker

HNF4α

p63 Invasive mucinous adenocarcinoma

But the issue is… • How to make judge for small biopsy? • How about frozen? Do lobectomy + LN dissection? NEED IMMUNO?? or wedge only? Mutation may not separate them!

CMPT. Some are early IMA? Miyai K et al. Pathol Int 2018 Well, may not be….

However!!! Recent Publication from MSKCC • The new concept of “ Bronchial Adenoma ” for all similar conditions. • There are several cases not completely fit to the criteria of CMPT. (lack mucous, cilia, papillary structure…) • But share most of molecular abnormality and clinical pictures.

Chang et al, AJSP 2018

Chang et al, AJSP 2018

Take Home Message: • CMPT is a newly recognized lung neoplasm • Diagnosis by small biopsy is challenging • Frozen to judge segmentectomy vs. lobectomy is difficult • Key is a presence of basal cells. (Do p63/p40) • May better to be included in “Bronchial adenoma”(?) • Mutation is frequent and gene analysis may not distinguish BA(CMPT) and IMA (except BRAF)

Nagasaki Univ Awaji Medical Center Thank you for your attention International Kameda Digital collaborators Pathology Lab