Adenocarcinoma in situ of the lung

The genes mutated in AIS differ based on exposure to tobacco smoke. Non-smokers with AIS commonly have mutations in EGFR (a driver) or HER2 (an important oncogene), or a gene fusion with ALK or ROS1 as one of the elements.{{cite book|title=World Cancer Report 2014|date=2014|publisher=World Health Organization|isbn=978-9283204299|pages=Chapter 5.1}}

Nonmucinous AIS is thought to derive from a transformed cell in the distal airways and terminal respiratory units, and often shows features of club cell or Type II pneumocyte differentiation. Mucinous AIS, in contrast, probably derives from a transformed glandular cell in distal bronchioles.{{cite journal |vauthors=Chilosi M, Murer B |title=Mixed adenocarcinomas of the lung: place in new proposals in classification, mandatory for target therapy |journal=Arch. Pathol. Lab. Med. |volume=134 |issue=1 |pages=55–65 |date=January 2010 |pmid=20073606 |doi=10.5858/134.1.55 |url=http://www.archivesofpathology.org/doi/full/10.1043/1543-2165-134.1.55}}

A multi-step carcinogenesis hypothesis suggests a progression from pulmonary atypical adenomatous hyperplasia (AAH) through AIS to invasive adenocarcinoma (AC), but to date this has not been formally demonstrated.{{Cite journal|last1=Bettio|first1=D|last2=Cariboni|first2=U|last3=Venci|first3=A|last4=Valente|first4=M|last5=Spaggiari|first5=P|last6=Alloisio|first6=M|year=2012|title=Cytogenetic findings in lung cancer that illuminate its biological history from adenomatous hyperplasia to bronchioalveolar carcinoma to adenocarcinoma: A case report|journal=Experimental and Therapeutic Medicine|volume=4|issue=6|pages=1032–1034|doi=10.3892/etm.2012.725|pmc=3494121|pmid=23226769}}

Type-I cystic adenomatoid malformation (CAM) has recently been identified as a precursor lesion for the development of mucinous AIS, but these cases are rare.{{cite journal |vauthors=Scialpi M, Cappabianca S, Rotondo A |title=Pulmonary congenital cystic disease in adults. Spiral computed tomography findings with pathologic correlation and management |journal=Radiol Med |volume=115 |issue=4 |pages=539–50 |date=June 2010 |pmid=20058095 |doi=10.1007/s11547-010-0467-6 |s2cid=7308576 |display-authors=etal}}{{cite journal |vauthors=Abecasis F, Gomes Ferreira M, Oliveira A, Vaz Velho H |title=[Bronchioloalveolar carcinoma associated with congenital pulmonary airway malformation in an asymptomatic adolescent] |language=Portuguese |journal=Rev Port Pneumol |volume=14 |issue=2 |pages=285–90 |year=2008 |pmid=18363023 |doi=10.1016/S0873-2159(15)30236-1 |doi-access=free }}

Rarely, AIS may develop a rhabdoid morphology due to the development of dense perinuclear inclusions.{{cite journal |vauthors=Song DE, Jang SJ, Black J, Ro JY |title=Mucinous bronchioloalveolar carcinoma of lung with a rhabdoid component—report of a case and review of the literature |journal=Histopathology |volume=51 |issue=3 |pages=427–30 |date=September 2007 |pmid=17727492 |doi=10.1111/j.1365-2559.2007.02784.x |s2cid=29727857 }}

The criteria for diagnosing pulmonary adenocarcinoma have changed considerably over time.{{cite book |author1=Kreyberg, L. |author2=Liebow, A.A. |author3=Uehlinger, E.A. |author4=World Health Organization. |title=Histological Typing of Lung Tumours |publisher=World Health Organization |location=Geneva, Switzerland |year=1967 |series=International histological classification of tumours, no. 1 |edition=1st |oclc=461784}}{{cite book |author =World Health Organization |title=Histological Typing of Lung Tumours |publisher=World Health Organization |location=Geneva, Switzerland |year=1981 |series=International histological classification of tumours, no. 1 |isbn=978-92-4-176101-7 |oclc=476258805 |edition=2nd}} The 2011 IASLC/ATS recommendations, adopted in the 2015 WHO guidelines, use the following criteria for adenocarcinoma in situ: Travis, W.D.; Colby, T.V.; Corrin, B.; et al.{{cite book |title=Histological Typing of Lung and Pleural Tumors |publisher=Springer |location=Berlin |year=1999 |isbn=978-3-540-65219-9 |series=International histological classification of tumours, no. 1 |edition=3rd}}

• tumor ≤3 cm
• solitary tumor
• pure "lepidic" growth*{{cite journal |last1=Iwata |first1=H |title=Adenocarcinoma containing lepidic growth. |journal=Journal of Thoracic Disease |date=September 2016 |volume=8 |issue=9 |pages=E1050–E1052 |doi=10.21037/jtd.2016.08.78 |pmid=27747060|pmc=5059295 |doi-access=free }}
• No stromal, vascular, or pleural invasion
• No histologic patterns of invasive adenocarcinoma
• No spread through air spaces
• Cell type mostly nonmucinous
• Minimal/absent nuclear atypia
• ± septal widening with sclerosis/elastosis

* lepidic = (i.e. scaly covering) growth pattern along pre-existing airway structures

By this standard, AIS cannot be diagnosed according to core biopsy or cytology sampling. Recommended practice is to report biopsy findings previously classified as nonmucinous BAC as adenocarcinoma with lepidic pattern, and those previously classified as mucinous BAC as mucinous adenocarcinoma.{{Cite web|url=https://www.thoracic.org/statements/resources/lcod/adenocarcinoma.pdf|title=IASLC/ATS/ERS International Multidisciplinary Classification of Lung Adenocarcinoma (2011)|last=Travis|display-authors=et al|date=2011|website=www.thoracic.org|access-date=March 10, 2018}}

The most recent 2015 World Health Organization (WHO) and 2011 International Association for the Study of Lung Cancer (IASLC) / American Thoracic Society (ATS) guidelines refine pulmonary adenocarcinoma subtypes in order to correspond to advances in personalized cancer treatment.{{Cite journal|last1=Travis|first1=William D.|last2=Brambilla|first2=Elisabeth|last3=Nicholson|first3=Andrew G.|last4=Yatabe|first4=Yasushi|last5=Austin|first5=John H.M.|last6=Beasley|first6=Mary Beth|last7=Chirieac|first7=Lucian. R.|last8=Dacic|first8=Sanja|last9=Duhig|first9=Edwina|title=The 2015 World Health Organization Classification of Lung Tumors|journal=Journal of Thoracic Oncology|volume=10|issue=9|pages=1243–1260|doi=10.1097/jto.0000000000000630|pmid=26291008|year=2015|doi-access=free}}

AIS is considered a pre-invasive malignant lesion that, after further mutation and progression, is thought to progress into an invasive adenocarcinoma. Therefore, it is considered a form of carcinoma in situ (CIS).

There are other classification systems that have been proposed for lung cancers. The Noguchi classification system for small adenocarcinomas has received considerable attention, particularly in Japan, but has not been nearly as widely applied and recognized as the WHO system.{{cite journal|display-authors=etal|vauthors=Noguchi M, Morikawa A, Kawasaki M|date=June 1995|title=Small adenocarcinoma of the lung. Histologic characteristics and prognosis|journal=Cancer|volume=75|issue=12|pages=2844–52|doi=10.1002/1097-0142(19950615)75:12<2844::aid-cncr2820751209>3.0.co;2-#|pmid=7773933|s2cid=196359177 }}

AIS may be further subclassified by histopathology, by which there are two major variants:

• mucinous (20–25% of cases){{cite journal |vauthors=Yousem SA, Beasley MB |title=Bronchioloalveolar carcinoma: a review of current concepts and evolving issues |journal=Arch. Pathol. Lab. Med. |volume=131 |issue=7 |pages=1027–32 |date=July 2007 |pmid=17616987 |doi=10.5858/2007-131-1027-BCAROC |url=http://www.archivesofpathology.org/doi/full/10.1043/1543-2165(2007)131[1027:BCAROC]2.0.CO;2}}{{cite journal |vauthors=Raz DJ, He B, Rosell R, Jablons DM |title=Current concepts in bronchioloalveolar carcinoma biology |journal=Clin. Cancer Res. |volume=12 |issue=12 |pages=3698–704 |date=June 2006 |pmid=16778095 |doi=10.1158/1078-0432.CCR-06-0457 |s2cid=17340788 |url=http://clincancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=16778095|doi-access=free }}
• non mucinous (75–80% of cases){{cite journal |vauthors=Lee KS, Kim Y, Han J, Ko EJ, Park CK, Primack SL |title=Bronchioloalveolar carcinoma: clinical, histopathologic, and radiologic findings |journal=Radiographics |volume=17 |issue=6 |pages=1345–57 |date=1 November 1997|pmid=9397450 |doi=10.1148/radiographics.17.6.9397450}}

This information is mostly in reference to the now outdated entity of BAC, which included some invasive forms of disease.

The treatment of choice in any patient with BAC is complete surgical resection, typically via lobectomy or pneumonectomy, with concurrent ipsilateral lymphadenectomy.

Non-mucinous BAC are highly associated with classical EGFR mutations, and thus are often responsive to targeted chemotherapy with erlotinib and gefitinib. K-ras mutations are rare in nm-BAC.{{cite journal |vauthors=Finberg KE, Sequist LV, Joshi VA |title=Mucinous differentiation correlates with absence of EGFR mutation and presence of KRAS mutation in lung adenocarcinomas with bronchioloalveolar features |journal=J Mol Diagn |volume=9 |issue=3 |pages=320–6 |date=July 2007 |pmid=17591931 |pmc=1899415 |doi=10.2353/jmoldx.2007.060182 |display-authors=etal}}

Mucinous BAC, in contrast, is much more highly associated with K-ras mutations and wild-type EGFR, and are thus usually insensitive to the EGFR tyrosine kinase inhibitors.{{cite journal |vauthors=Sakuma Y, Matsukuma S, Yoshihara M |title=Distinctive evaluation of nonmucinous and mucinous subtypes of bronchioloalveolar carcinomas in EGFR and K-ras gene-mutation analyses for Japanese lung adenocarcinomas: confirmation of the correlations with histologic subtypes and gene mutations |journal=Am. J. Clin. Pathol. |volume=128 |issue=1 |pages=100–8 |date=July 2007 |pmid=17580276 |doi=10.1309/WVXFGAFLAUX48DU6 |url=http://ajcp.ascpjournals.org/cgi/pmidlookup?view=long&pmid=17580276|display-authors=etal|doi-access=free }} In fact, there is some evidence that suggests that the administration of EGFR-pathway inhibitors to patients with K-ras mutated BAC may even be harmful.{{cite journal |author =Vincent MD |title=Optimizing the management of advanced non-small-cell lung cancer: a personal view |journal=Curr Oncol |volume=16 |issue=4 |pages=9–21 |date=August 2009 |pmid=19672420 |pmc=2722061 |doi=10.3747/co.v16i4.465}}

This information is mostly in reference to the now outdated entity of BAC, which included some invasive forms of disease.

Taken as a class, long-term survival rates in BAC tend to be higher than those of other forms of NSCLC.{{cite journal |vauthors=Breathnach OS, Kwiatkowski DJ, Finkelstein DM |title=Bronchioloalveolar carcinoma of the lung: recurrences and survival in patients with stage I disease |journal=J. Thorac. Cardiovasc. Surg. |volume=121 |issue=1 |pages=42–7 |date=January 2001 |pmid=11135158 |doi=10.1067/mtc.2001.110190 |display-authors=etal|doi-access=free }}{{cite journal |vauthors=Grover FL, Piantadosi S |title=Recurrence and survival following resection of bronchioloalveolar carcinoma of the lung--The Lung Cancer Study Group experience |journal=Ann. Surg. |volume=209 |issue=6 |pages=779–90 |date=June 1989 |pmid=2543339 |pmc=1494125 |doi=10.1097/00000658-198906000-00016}} BAC generally carries a better prognosis than other forms of NSCLC, which can be partially attributed to localized presentation of the disease. Though other factors might play a role. Prognosis of BAC depends upon the histological subtype and extent at presentation but are generally same as other NSCLC.{{cite journal|last1=Barkley|first1=JE|last2=Green|first2=MR|title=Bronchioloalveolar carcinoma.|journal=Journal of Clinical Oncology|date=August 1996|volume=14|issue=8|pages=2377–86|pmid=8708731|doi=10.1200/jco.1996.14.8.2377}}

Recent research has made it clear that nonmucinous and mucinous BAC are very different types of lung cancer.{{cite journal |vauthors=Garfield DH, Cadranel J, West HL |title=Bronchioloalveolar carcinoma: the case for two diseases |journal=Clin Lung Cancer |volume=9 |issue=1 |pages=24–9 |date=January 2008 |pmid=18282354 |doi=10.3816/CLC.2008.n.004 }} Mucinous BACis much more likely to present with multiple unilateral tumors and/or in a unilateral or bilateral pneumonic form than nonmucinous AIS . The overall prognosis for patients with mucinous AIS is significantly worse than patients with nonmucinous AIS .{{cite journal |vauthors=Furák J, Troján I, Szoke T |title=Bronchioloalveolar lung cancer: occurrence, surgical treatment and survival |journal=Eur J Cardiothorac Surg |volume=23 |issue=5 |pages=818–23 |date=May 2003 |pmid=12754039 |doi=10.1016/s1010-7940(03)00084-8|display-authors=etal|doi-access=free }}

Although data are scarce, some studies suggest that survival rates are even lower in the mixed mucinous/non-mucinous variant than in the monophasic forms.

In non-mucinous BAC, neither club cell nor type II pneumocyte differentiation appears to affect survival or prognosis.

When BAC recurs after surgery, the recurrences are local in about three-quarters of cases, a rate higher than other forms of NSCLC, which tends to recur distantly.

Information about the epidemiology of AIS is limited, due to changes in definition of this disease and separation from BAC category.

Under the new, more restrictive WHO criteria for lung cancer classification, AIS is now diagnosed much less frequently than it was in the past.{{cite book|url=http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-cover.pdf|title=Pathology and Genetics of Tumours of the Lung, Pleura, Thymus and Heart|publisher=IARC Press|year=2004|isbn=978-92-832-2418-1|editor1-last=Travis|editor1-first=William D|series=World Health Organization Classification of Tumours|location=Lyon|access-date=27 March 2010|editor2-last=Brambilla|editor2-first=Elisabeth|editor3-last=Muller-Hermelink|editor3-first=H Konrad|editor4-last=Harris|editor4-first=Curtis C|archive-url=https://web.archive.org/web/20090823210304/http://www.iarc.fr/en/publications/pdfs-online/pat-gen/bb10/bb10-cover.pdf|archive-date=2009-08-23|url-status=dead}} Recent studies suggest that AIS comprises between 3% and 5% of all lung carcinomas in the U.S.{{cite journal|vauthors=Zell JA, Ou SH, Ziogas A, Anton-Culver H|s2cid=32004708|date=November 2005|title=Epidemiology of bronchioloalveolar carcinoma: improvement in survival after release of the 1999 WHO classification of lung tumors|journal=J. Clin. Oncol.|volume=23|issue=33|pages=8396–405|doi=10.1200/JCO.2005.03.0312|pmid=16293870|url=https://escholarship.org/uc/item/0sc2k36f|doi-access=free}}{{cite journal |vauthors=Read WL, Page NC, Tierney RM, Piccirillo JF, Govindan R |title=The epidemiology of bronchioloalveolar carcinoma over the past two decades: analysis of the SEER database |journal=Lung Cancer |volume=45 |issue=2 |pages=137–42 |date=August 2004 |pmid=15246183 |doi=10.1016/j.lungcan.2004.01.019 }}

The incidence of bronchiolo-alveolar carcinoma has been reported to vary from 4–24% of all lung cancer patients. An analysis of Surveillance epidemiology and End results registry ( SEER) by Read et al. revealed that although the incidence of BAC has increased over the past two decade it still constitutes less than 4% of NSCLC in every time interval. This difference in the incidence has been attributed to complex histopathology of cancer. While pure BAC is rare, the increase in incidence as seen in various studies can be due to unclear histological classification till WHO came up with its classification in 1999 and then in 2004.

Another distinguishing feature about BAC is that it afflicts men and women in equal proportions, some recent studies even suggest slightly higher incidence among women.

The criteria for classifying lung cancer have changed considerably over time, becoming progressively more restrictive.

In 2011, the IASLC/ATS/ERS classification recommended discontinuing the BAC classification altogether, as well as the category of mixed subtype adenocarcinoma. This change was made because the term BAC was being broadly applied to small solitary noninvasive tumors, minimally invasive adenocarcinoma, mixed subtype invasive adenocarcinoma, and even widespread disease. In addition to creating the new AIS and minimally-invasive categories, the guidelines recommend new terminology to clearly denote predominantly-noninvasive adenocarcinoma with mild invasion (lepidic predominant adenocarcinoma), as well as invasive mucinous adenocarcinoma in place of mucinous BAC.

Mucinous BAC

Image:Brochiolo-alveolar carcinoma with mucin production (1).jpg

Image:Brochiolo-alveolar carcinoma with mucin production (2).jpg

Image:Bronchioloalveolar carcinoma, mucinous type.jpg

Image:Bronchioloalveolar carcinoma, mucinous type 2.jpg

Non-mucinous BAC

File:Nonmucinous_bronchioloalveolar_carcinoma.jpg

• Atypical adenomatous hyperplasia of the lung
• Minimally invasive adenocarcinoma of the lung
• Adenocarcinoma of the lung

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{{Medical resources

| DiseasesDB =

| ICD10 = {{ICD10|C|34}}

| ICD9 = {{ICD9|162}}

| ICDO = {{ICDO|8250|3}}

| OMIM =

| MedlinePlus =

| eMedicineSubj =

| eMedicineTopic =

| MeshID = D002282

}}

{{Respiratory tract neoplasia}}

{{DEFAULTSORT:Bronchioloalveolar Carcinoma}}

Category:Rare cancers

Category:Lung cancer

Category:Histopathology

2023 American association thoracic surgery AATS expert consensus document management subsolid lung nodules general thoracic and Cardiovascular surgery 2024 Chen et al, you could check this for updating what you got which isn't really too good actually and then the other thing is this thing about the big surgery instead of the wedge resection you might want to check whether wedges the general standard which it is so since wedge it is classified as sublobar you might want to change that