Lung
Adenocarcinoma
Invasive mucinous
Author: Akira Yoshikawa, M.D.
Editorial Board Member: Andrey Bychkov, M.D., Ph.D.
Editor-in-Chief: Debra L. Zynger, M.D.
Last author update: 4 September 2020
Last staff update: 1 June 2022
Copyright: 2020-2024, PathologyOutlines.com, Inc.
PubMed Search: Invasive mucinous adenocarcinoma lung
Table of Contents
Definition / general | Essential features | Terminology | ICD coding | Epidemiology | Sites | Pathophysiology | Etiology | Diagrams / tables | Clinical features | Diagnostic criteria | Radiology description | Radiology images | Prognostic factors | Case reports | Treatment | Gross description | Gross images | Microscopic (histologic) description | Microscopic (histologic) images | Cytology description | Cytology images | Positive stains | Negative stains | Molecular / cytogenetics description | Sample pathology report | Differential diagnosis | Board review style question #1 | Board review style answer #1 | Board review style question #2 | Board review style answer #2Cite this page: Yoshikawa A. Invasive mucinous. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/lungtumorinvmucadenocarcinoma.html. Accessed April 20th, 2024.
Definition / general
- Distinct variant of lung adenocarcinoma with a goblet or columnar morphology and abundant intracytoplasmic mucin
Essential features
- Rare variant of lung adenocarcinoma with a goblet or columnar morphology and abundant intracytoplasmic mucin
- No criteria regarding percentage of cells with mucin but typically homogeneous and not admixed with nonmucinous glands
- Aggressive clinical behavior often associated with intrapulmonary metastasis and recurrence
Terminology
- Colloid adenocarcinoma is currently thought to be in a separate entity according to molecular and genetic differences (J Pathol Clin Res 2017;3:139, J Thorac Oncol 2011;6:244, Transl Lung Cancer Res 2017;6:234, Am J Surg Pathol 2014;38:1118)
ICD coding
Epidemiology
- 0.2% of primary lung cancer (J Thorac Dis 2018;10:3595)
- 3 - 10% of all lung adenocarcinoma (J Thorac Oncol 2016;11:1064, Hum Pathol 2018;71:8, Histopathology 2018;73:38, Am J Surg Pathol 2014;38:1118)
- M:F = 1:2
Sites
- Lung; lower lobe predominant (J Thorac Dis 2018;10:3595)
Pathophysiology
- Associated with Ras-Raf-MEK-ERK pathway (Hum Pathol 2018;71:8, Am J Surg Pathol 2014;38:1118)
- KRAS mutation in 57 - 73%
- ALK rearrangement in minor cases
- Rare EGFR mutation
Etiology
- Less associated with smoking than other subtypes of lung adenocarcinoma
Diagrams / tables
Images hosted on other servers:
Survival curves
Clinical features
- Frequent intrapulmonary metastasis and recurrence
- Rare extrapulmonary and distant metastasis (J Thorac Dis 2018;10:3595)
- 80% are N0 at the time of diagnosis (versus 55% in nonmucinous adenocarcinoma)
- 80% are M0 at the time of diagnosis (versus 55% in nonmucinous adenocarcinoma)
- Larger size and higher T category at presentation
Diagnostic criteria
- Based on histological and immunohistochemical features
- Even if pathological results correspond to primary invasive mucinous adenocarcinoma of lung, colorectal adenocarcinoma must be ruled out by endoscopy and radiology
Radiology description
- Consolidation with various appearance (Eur J Radiol 2015;84:993, Cancer Imaging 2019;19:47)
- Solid lesion similar to other lung cancers
- Mixed solid and gland glass opacity lesion similar to pneumonia
- Air bronchogram is common
- Often multifocal with multilobar involvement
- FDG-PET often demonstrates relatively low accumulation to the lesion
Radiology images
Images hosted on other servers:
Computed tomography
Prognostic factors
- Intermediate to poor prognosis compared with nonmucinous adenocarcinoma (Hum Pathol 2018;71:8, J Thorac Dis 2018;10:3595, Lung Cancer 2017;109:14, J Thorac Oncol 2016;11:1064, J Thorac Oncol 2015;10:1156)
- Approximately 70% spread through air space, which is associated with higher recurrence
Case reports
- 19 year old woman with invasive mucinous adenocarcinoma (Asian Cardiovasc Thorac Ann 2018;26:635)
- 50 year old woman with invasive mucinous adenocarcinoma treated by radioablation (J Radiol Case Rep 2013;7:15)
- 62 year old woman with invasive mucinous adenocarcinoma having targetable NRG1 fusion (J Thorac Oncol 2017;12:e200)
- 68 year old man with invasive mucinous adenocarcinoma arising in a type 1 congenital pulmonary airway malformation (Acta Chir Belg 2019;1)
- 81 year old man with invasive mucinous adenocarcinoma harboring EGFR mutation (Surg Today 2015;45:1330)
Treatment
- Same as nonmucinous adenocarcinoma
- NCCN Guidelines 3.2018
- For stages I, II, IIA: surgical resection (preferred) + adjuvant chemotherapy (platinum based) and radiation
- Inoperable or metastatic: chemotherapy variable radiation
Gross description
- Gray to yellowish appearance
- Solid lesion with a gradational and ill defined border
- Mucus production inside and around the lesion
- Reference: Leslie: Practical Pulmonary Pathology - A Diagnostic Approach, 3rd edition, 2017
Gross images
Contributed by Akira Yoshikawa, M.D. and Yale Rosen, M.D.
Invasive mucinous adenocarcinoma
Invasive, diffuse
Lepidic growth pattern
Microscopic (histologic) description
- Goblet cells or GI tract type columnar cells
- No criteria regarding percentage of cells with mucin but typically homogeneous and not admixed with nonmucinous glands
- Abundant intracytoplasmic mucin
- Basally oriented nuclei with minimal atypia
- Adjacent alveolar lumens are often filled with mucin (not specific for invasive mucinous adenocarcinoma)
- Tend to be well differentiated (J Thorac Dis 2018;10:3595)
- Often predominantly lepidic growth with slight distortion / destruction of alveolar architecture
- Admixed with minor papillary, acinar or micropapillary component
- Spread through air space is common
Microscopic (histologic) images
Contributed by Akira Yoshikawa, M.D.
Intraalveolar mucin
Nodules with fibrosis
Tumor periphery
Diffuse spread
Acinar growth pattern
Admixed pneumocytes
Abundant apical mucin
Extracellular and apical mucin
HNF4α
TTF1 / Napsin A
Contributed by @zaalruwai83 on Twitter
Invasive mucinous adenocarcinoma
Cytology description
- Sheets or papillary clusters of high columnar cells (Bibbo: Comprehensive Cytopathology, 4th edition, 2014)
- Abundant intracytoplasmic mucin ("gold mucin")
- Relatively small nuclei with minimal atypia
Cytology images
Contributed by Takashi Hori, C.T. and Akira Yoshikawa, M.D.
Cluster of tumor cells
Gold mucin
Papillary cluster
Positive stains
- PAS: intracellular and extracellular mucin
- HNF4α: > 90% (but also in adenocarcinoma of other origins like stomach, intestine, pancreas, ovary, uterus, cervix) (Am J Surg Pathol 2013;37:211)
- MUC2 (but also positive in adenocarcinoma of other origins like GI tract) (Am J Surg Pathol 2004;28:442)
- CK7
Negative stains
- TTF1, Napsin A: can be very weakly or focally positive in rare cases
- CDX2: variable results from different reports; per own experience, negative or rarely faintly positive (J Thorac Oncol 2011;6:244, Am J Surg Pathol 2004;28:442, Am J Surg Pathol 2013;37:211)
- CK20: equivocal, variable results from different institutions
Molecular / cytogenetics description
- HNF4α positive mucinous adenocarcinoma is often associated with KRAS or EGFR (< 5%) mutations (Am J Surg Pathol 2013;37:211)
- Some cases with HNF4α negative mucinous adenocarcinoma is associated with ALK fusion (Am J Surg Pathol 2013;37:211)
- Other mutations in KRAS negative cases include NRG1, ERBB4 and BRAF fusions (Clin Cancer Res 2014;20:3087)
Sample pathology report
- Lung, right upper lobe, resection:
- Invasive mucinous adenocarcinoma (see synoptic report)
Differential diagnosis
- Metastatic colorectal adenocarcinoma:
- Colloid adenocarcinoma (Hum Pathol 2015;46:836):
- Marked mucin pool replacing normal parenchyma
- Neoplastic epithelium floating in the mucin
- Fragments of displaced alveolar walls
- Minimal nuclear atypia
- Fibrotic encapsulation in minor cases (formerly called cystadenocarcinoma)
Board review style question #1
This patient had multifocal pulmonary lesions. CK20 was positive. Which other marker substantiates the diagnosis and would likely be expressed?
- TTF1
- PAS
- Alcian blue
- EpCAM
- CDX2
Board review style answer #1
E. This is metastatic colorectal adenocarcinoma which usually expresses CDX2 and CK20.
Comment Here
Reference: Invasive mucinous adenocarcinoma
Comment Here
Reference: Invasive mucinous adenocarcinoma
Board review style question #2
Which of the following findings specifically corresponds to invasive mucinous adenocarcinoma of the lung compared with other sybtypes of lung adenocarcinoma?
- Abundant mucin in air spaces
- Abundant intracytoplasmic mucin
- TTF1 positive
- Napsin A positive
- p40 positive
Board review style answer #2
