Bronchioloalveolar carcinoma: Difference between revisions
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=== Minimally invasive adenocarcinoma (MIA) === | === Minimally invasive adenocarcinoma (MIA) === | ||
* Less than or equal to 3 cm | * Less than or equal to 3 cm | ||
* Less than or equal to 5 mm area of stromal invasion or | * Less than or equal to 5 mm area of stromal invasion or another type of growth patterns (in comparison with the lepidic pattern of growth) | ||
* Can be mucinous, | * Can be mucinous, nonmucinous or mixed | ||
=== Invasive adenocarcinoma === | === Invasive adenocarcinoma === | ||
* Presence of stromal invasion or patterns of growth other than lepidic | * Presence of stromal invasion or patterns of growth other than lepidic | ||
* Lepidic predominant - Type of invasive adenocarcinoma with more than 5 mm invasion (Previously known as Non Mucinous BAC with invasion) | * Lepidic predominant - Type of invasive adenocarcinoma with more than 5 mm invasion (Previously known as Non-Mucinous BAC with invasion) | ||
* Invasive mucinous adenocarcinoma - Previously known as mucinous BAC | * Invasive mucinous adenocarcinoma - Previously known as mucinous BAC | ||
| Line 63: | Line 63: | ||
* More often seen in non-smokers | * More often seen in non-smokers | ||
* Develop from bronchiolar epithelial metaplasia | * Develop from bronchiolar epithelial metaplasia | ||
* Present | * Present often as pneumonia-like infiltrate | ||
* Frequently associated with a K-Ras mutation | * Frequently associated with a K-Ras mutation | ||
| Line 69: | Line 69: | ||
* More common | * More common | ||
* More often seen in smokers | * More often seen in smokers | ||
* Originate from the terminal respiratory cells, type II pneumocytes and | * Originate from the terminal respiratory cells, type II pneumocytes, and Clara cells | ||
* Presents usually as a ground glass opacity | * Presents usually as a ground glass opacity | ||
* Frequently associated with EFGR mutations | * Frequently associated with EFGR mutations | ||
==Pathophysiology== | ==Pathophysiology== | ||
Bronchioloalveolar carcinoma or lepidic predominant adenocarcinoma develops in the cells near the alveoli (including type II pneumocytes and Clara cells) in the terminal or outer portion of the lungs. | |||
===Microscopic Pathology=== | ===Microscopic Pathology=== | ||
| Line 83: | Line 83: | ||
* Almost 30 percent patients of BAC are never smokers as compared to adenocarcinoma's (15 percent are never smokers) and squamous cell cancers (only 5 percent are never smokers)<ref name="pmid22814813">{{cite journal| author=Bracci PM, Sison J, Hansen H, Walsh KM, Quesenberry CP, Raz DJ et al.| title=Cigarette smoking associated with lung adenocarcinoma in situ in a large case-control study (SFBALCS). | journal=J Thorac Oncol | year= 2012 | volume= 7 | issue= 9 | pages= 1352-60 | pmid=22814813 | doi=10.1097/JTO.0b013e31825aba47 | pmc=3421052 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22814813 }}</ref> | * Almost 30 percent patients of BAC are never smokers as compared to adenocarcinoma's (15 percent are never smokers) and squamous cell cancers (only 5 percent are never smokers)<ref name="pmid22814813">{{cite journal| author=Bracci PM, Sison J, Hansen H, Walsh KM, Quesenberry CP, Raz DJ et al.| title=Cigarette smoking associated with lung adenocarcinoma in situ in a large case-control study (SFBALCS). | journal=J Thorac Oncol | year= 2012 | volume= 7 | issue= 9 | pages= 1352-60 | pmid=22814813 | doi=10.1097/JTO.0b013e31825aba47 | pmc=3421052 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22814813 }}</ref> | ||
* However some recent pooled studies have shown a two-fold increased risk of BAC in smokers as compared to never-smokers and higher risk with increasing and prolonged consumption with risk decreasing in years following the smoking cessation<ref name="pmid21072579">{{cite journal| author=Boffetta P, Jayaprakash V, Yang P, Asomaning K, Muscat JE, Schwartz AG et al.| title=Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO). | journal=Cancer Causes Control | year= 2011 | volume= 22 | issue= 1 | pages= 73-9 | pmid=21072579 | doi=10.1007/s10552-010-9676-5 | pmc=3002160 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21072579 }}</ref> | * However some recent pooled studies have shown a two-fold increased risk of BAC in smokers as compared to never-smokers and higher risk with increasing and prolonged consumption with risk decreasing in years following the smoking cessation<ref name="pmid21072579">{{cite journal| author=Boffetta P, Jayaprakash V, Yang P, Asomaning K, Muscat JE, Schwartz AG et al.| title=Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO). | journal=Cancer Causes Control | year= 2011 | volume= 22 | issue= 1 | pages= 73-9 | pmid=21072579 | doi=10.1007/s10552-010-9676-5 | pmc=3002160 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21072579 }}</ref> | ||
* Still, the magnitude of relationship between smoking and adenocarcinoma in situ (BAC) is much smaller than other lung cancers and further studies are needed on this | * Still, the magnitude of the relationship between smoking and adenocarcinoma in situ (BAC) is much smaller than other lung cancers and further studies are needed on this | ||
=== Genetics: === | === Genetics: === | ||
| Line 110: | Line 110: | ||
===Gender === | ===Gender === | ||
*Women are more commonly affected | *Women are more commonly affected by BAC than males. | ||
===Race=== | ===Race=== | ||
Revision as of 17:53, 30 October 2018
Synonyms and keywords: Synonym 1; Synonym 2; Synonym 3
| Bronchioloalveolar carcinoma | |
| MeSH | D002282 |
|---|---|
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Anila Hussain, MD [2] Manpreet Kaur, MD [3]
Overview
- Bronchioloalveolar carcinoma (BAC) is a rare type of lung cancer which more frequently among never-smokers, women and Asians( particularly Eastern-Asian).[1]
- According to the new WHO classification, Bronchioloalveloar Carcinoma (BAC) is now classified as a subtype of lung adenoacarcinoma and the term BAC is no longer in use[2].
- It is also known as "lepidic predominant adenocarcinoma" due to its progression along the alveolar walls without invading stromal, pleural or vascular tissue[3]
- By definition, BAC is not an invasive tumor. Therefore, pathologists classify it as a form of carcinoma in situ (CIS). However, unlike other forms of CIS, its behavior is malignant, often lethal. Major surgery, either a lobectomy or a pneumonectomy, is needed to control it, and recurrences are frequent. For this reason, oncologists classify it among the other malignant tumors, which are invasive tumors.
Historical prespective
- Bronchioloalveolar carcinoma was first discovered by Dr. Averill Liebow, in the year of 1960.
- In 1999, the World Health Organization has given the term 'Pure BAC' as a subtype of adenocarcinoma that doesn’t Invade.
- In [year], [gene] mutations were first identified in the pathogenesis of [disease name].
- In [year], the first [discovery] was developed by [scientist] to treat/diagnose [disease name].
Classification
According to the current criteria, bronchioloalveolar carcinoma is Pas a sub-type of lung adenocarcinoma and the lesions are now described under categories adenocarcinoma in Situ (AIS) and minimally invasive adenocarcinoma (MIA)[4].
However it is distinct from other lung adenocarcinomas by different clinical features, prognosis and response to treatment.[5]
IASLC/ATS/ERS Classification of Lung Adenocarcinoma in Resection Specimens describes BAC in following subheadings[6];
Adenocarcinoma in situ (AIS) - Previously Known as solitary BAC
- Less than or equal to 3 cm
- Can be either mucinous or serous
- No stromal, lymphatic, or pleural invasion
- No necrosis
- no other growth pattern other than along the airways (lepidic)
Minimally invasive adenocarcinoma (MIA)
- Less than or equal to 3 cm
- Less than or equal to 5 mm area of stromal invasion or another type of growth patterns (in comparison with the lepidic pattern of growth)
- Can be mucinous, nonmucinous or mixed
Invasive adenocarcinoma
- Presence of stromal invasion or patterns of growth other than lepidic
- Lepidic predominant - Type of invasive adenocarcinoma with more than 5 mm invasion (Previously known as Non-Mucinous BAC with invasion)
- Invasive mucinous adenocarcinoma - Previously known as mucinous BAC
The two different sub-types of BAC depending on the cellular cytology are described as follows[7];
Mucinous BAC:
- Less common
- More often seen in non-smokers
- Develop from bronchiolar epithelial metaplasia
- Present often as pneumonia-like infiltrate
- Frequently associated with a K-Ras mutation
Non-Mucinous BAC:
- More common
- More often seen in smokers
- Originate from the terminal respiratory cells, type II pneumocytes, and Clara cells
- Presents usually as a ground glass opacity
- Frequently associated with EFGR mutations
Pathophysiology
Bronchioloalveolar carcinoma or lepidic predominant adenocarcinoma develops in the cells near the alveoli (including type II pneumocytes and Clara cells) in the terminal or outer portion of the lungs.
Microscopic Pathology
Causes
Smoking:
- Smoking has not been thought to be associated with BAC generally
- Almost 30 percent patients of BAC are never smokers as compared to adenocarcinoma's (15 percent are never smokers) and squamous cell cancers (only 5 percent are never smokers)[8]
- However some recent pooled studies have shown a two-fold increased risk of BAC in smokers as compared to never-smokers and higher risk with increasing and prolonged consumption with risk decreasing in years following the smoking cessation[9]
- Still, the magnitude of the relationship between smoking and adenocarcinoma in situ (BAC) is much smaller than other lung cancers and further studies are needed on this
Genetics:
- Mucinous BAC are frequently associated with K-ras mutations
- Non-mucinous BAC are frequently associated with EFGR mutations
Hypothesis regarding JSRV[10]:
- Jaagsiekte Sheep Retrovirus (JSRV) is a highly infectious retrovirus in sheep that causes low grade tumors in sheep resembling BAC
- This led to the hypothesis that same virus might be responsible for the similar cancer in humans
- However, no molecular study has confirmed this hypothesis so far
Differentiating [disease name] from other Diseases
- [Disease name] must be differentiated from other diseases that cause [clinical feature 1], [clinical feature 2], and [clinical feature 3], such as:
- [Differential dx1]
- [Differential dx2]
- [Differential dx3]
Epidemiology and Demographics
- BAC is a rare form of lung cancer that comprises less than 4 percent of total cases of lung cancers
- Age adjusted Incidence rates were found to be between 1 or 2 per 100,000 in USA (1970's-1980's)[11]
- Rising incidence has been suggested by some studies in later years[12], however no marked increased in incidence rate was confirmed or reported to SEER database in the next 2 decades[13] (after 1980's)
Age
- BAC or AIS is thought to be more commonly seen in younger population, yet no evidence of such a pattern has been found in the studies and different studies have shown different results
- According to SEER database, mean age at diagnosis for BAC (years) is 66.99 +/- 10.66 which is very similar to other NSCLC and only 6.06 percent patients were found to be below 50 years of age[14]
Gender
- Women are more commonly affected by BAC than males.
Race
- BAC usually affects individuals of the Asians( particularly Eastern-Asian) ethnicity.
- White individuals are less likely to develop BAC or AIS.
Risk Factors
- Risk factors for development of BAC are poorly understood due to rarity of the type of cancer and recent change in WHO definition and classification
- Some common risk factors that can be considered in the development of BAC are smoking (not a confirmed risk factor) and genetic supectibility in certain ethnicities.
- Some single nucleotide polymorphisms (SNPs) are thought to be associated with AIS in certain ethnicities[15] (asian) and non smokers for example TERT-CLPMT1L region on Chr5p15 was found to be linked with adenocarcinoma risk in non-smoking asian women[16], however no study showed particular relation of genetic supectibility to BAC.
Natural History, Complications and Prognosis
- The patients with BAC may remain asymptomatic for years
- common clinical features include cough, sputum and shortness of breath.
- If left untreated, diffuse disease usually leads to death within the 3 years
- Common complications of [disease name] include [complication 1], [complication 2], and [complication 3].
- Prognosis is generally good, especially in case of localized disease in early stages[17]
- One study showed a 5 year prognosis of 100 percent after surgery in patients with tumors 3 cm or less[18]
- However, the prognosis vary according to stage of disease at the time of diagnosis
Prognostic Subgroups[19]
- Low grade
- 100 percent 5 year disease free survival
- Includes adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA)
- Intermediate grade
- Non-mucinous lepidic predominant - 90 percent 5 year disease free survival
- Papillary predominant - 83 percent 5 year disease free survival
- Acinar predominant - 84 percent 5 year disease free survival
- High grade
- Invasive mucinous adenocarcinoma - 75 percent 5-year disease-free survival
- Colloid predominant - 71 percent 5-year disease-free survival
- Solid predominant - 70 percent 5-year disease-free survival
- Micropapillary predominant - 67 percent 5-year disease-free survival
Diagnosis
Diagnostic Criteria
Symptoms
| Symptom | Percentage of Patients with the symptom |
|---|---|
| Cough | 35 |
| Sputum | 24 |
| Shortness of Breath | 15 |
| Weight loss | 13 |
| Hemoptysis | 11 |
| Fever | 8 |
| Bronchorrhea
(whitish mucoid or watery expectoration) |
5 |
Physical Examination
- Patients with [disease name] usually appear [general appearance].
- Physical examination may be remarkable for:
- [finding 1]
- [finding 2]
- [finding 3]
- [finding 4]
- [finding 5]
- [finding 6]
Laboratory Findings
- There are no specific laboratory findings associated with [disease name].
- A [positive/negative] [test name] is diagnostic of [disease name].
- An [elevated/reduced] concentration of [serum/blood/urinary/CSF/other] [lab test] is diagnostic of [disease name].
- Other laboratory findings consistent with the diagnosis of [disease name] include [abnormal test 1], [abnormal test 2], and [abnormal test 3].
Imaging Findings
- There are no [imaging study] findings associated with [disease name].
- [Imaging study 1] is the imaging modality of choice for [disease name].
- On [imaging study 1], [disease name] is characterized by [finding 1], [finding 2], and [finding 3].
- [Imaging study 2] may demonstrate [finding 1], [finding 2], and [finding 3].
Other Diagnostic Studies
- [Disease name] may also be diagnosed using [diagnostic study name].
- Findings on [diagnostic study name] include [finding 1], [finding 2], and [finding 3].
Treatment
Medical Therapy
- There is no treatment for [disease name]; the mainstay of therapy is supportive care.
- The mainstay of therapy for [disease name] is [medical therapy 1] and [medical therapy 2].
- [Medical therapy 1] acts by [mechanism of action 1].
- Response to [medical therapy 1] can be monitored with [test/physical finding/imaging] every [frequency/duration].
Surgery
- Surgery is the mainstay of therapy for [disease name].
- [Surgical procedure] in conjunction with [chemotherapy/radiation] is the most common approach to the treatment of [disease name].
- [Surgical procedure] can only be performed for patients with [disease stage] [disease name].
Prevention
- There are no primary preventive measures available for [disease name].
- Once diagnosed and successfully treated, patients with [disease name] are followed-up every [duration]. Follow-up testing includes [test 1], [test 2], and [test 3]. Effective measures for the primary prevention of [disease name] include [measure1], [measure2], and [measure3].
References
- ↑ Raz, DJ (Mar 2006). "Bronchioloalveolar carcinoma: a review". Clinical Lung Cancer. Cancer Information Group. 7 (5): 313–322. Unknown parameter
|coauthors=ignored (help) - ↑ Butt YM, Allen TC (2015). "The Demise of the Term Bronchioloalveolar Carcinoma". Arch Pathol Lab Med. 139 (8): 981–3. doi:10.5858/arpa.2013-0385-RA. PMID 26230592.
- ↑ Garfield DH, Cadranel J, West HL (2008). "Bronchioloalveolar carcinoma: the case for two diseases". Clin Lung Cancer. 9 (1): 24–9. doi:10.3816/CLC.2008.n.004. PMID 18282354.
- ↑ Travis, William D.; Brambilla, Elisabeth; Nicholson, Andrew G.; Yatabe, Yasushi; Austin, John H.M.; Beasley, Mary Beth; Chirieac, Lucian. R.; Dacic, Sanja; Duhig, Edwina; Flieder, Douglas B.; Geisinger, Kim; Hirsch, Fred R.; Ishikawa, Yuichi; Kerr, Keith M.; Noguchi, Masayuki; Pelosi, Giuseppe; Powell, Charles A.; Tsao, Ming Sound; Wistuba, Ignacio (2015). "The 2015 World Health Organization Classification of Lung Tumors". Journal of Thoracic Oncology. 10 (9): 1243–1260. doi:10.1097/JTO.0000000000000630. ISSN 1556-0864.
- ↑ Lee, KS (Nov–Dec 1997). "Bronchioloalveolar carcinoma: clinical, histopathologic, and radiologic findings" (PDF). RadioGraphics. 17 (6): 1345–1357. PMID 9397450. Retrieved 2007-12-03. Unknown parameter
|coauthors=ignored (help) - ↑ New Pathologic Classification of Lung Cancer: Relevance for Clinical Practice and Clinical Trials William D. Travis, Elisabeth Brambilla, and Gregory J. Riely Journal of Clinical Oncology 2013 31:8, 992-1001
- ↑ Garfield DH, Cadranel J, West HL (2008). "Bronchioloalveolar carcinoma: the case for two diseases". Clin Lung Cancer. 9 (1): 24–9. doi:10.3816/CLC.2008.n.004. PMID 18282354.
- ↑ Bracci PM, Sison J, Hansen H, Walsh KM, Quesenberry CP, Raz DJ; et al. (2012). "Cigarette smoking associated with lung adenocarcinoma in situ in a large case-control study (SFBALCS)". J Thorac Oncol. 7 (9): 1352–60. doi:10.1097/JTO.0b013e31825aba47. PMC 3421052. PMID 22814813.
- ↑ Boffetta P, Jayaprakash V, Yang P, Asomaning K, Muscat JE, Schwartz AG; et al. (2011). "Tobacco smoking as a risk factor of bronchioloalveolar carcinoma of the lung: pooled analysis of seven case-control studies in the International Lung Cancer Consortium (ILCCO)". Cancer Causes Control. 22 (1): 73–9. doi:10.1007/s10552-010-9676-5. PMC 3002160. PMID 21072579.
- ↑ Mornex JF, Thivolet F, De las Heras M, Leroux C (2003). "Pathology of human bronchioloalveolar carcinoma and its relationship to the ovine disease". Curr Top Microbiol Immunol. 275: 225–48. PMID 12596901.
- ↑ Falk RT, Pickle LW, Fontham ET, Greenberg SD, Jacobs HL, Correa P; et al. (1992). "Epidemiology of bronchioloalveolar carcinoma". Cancer Epidemiol Biomarkers Prev. 1 (5): 339–44. PMID 1339048.
- ↑ Barsky SH, Cameron R, Osann KE, Tomita D, Holmes EC (1994). "Rising incidence of bronchioloalveolar lung carcinoma and its unique clinicopathologic features". Cancer. 73 (4): 1163–70. PMID 8313318.
- ↑ Read WL, Page NC, Tierney RM, Piccirillo JF, Govindan R (2004). "The epidemiology of bronchioloalveolar carcinoma over the past two decades: analysis of the SEER database". Lung Cancer. 45 (2): 137–42. doi:10.1016/j.lungcan.2004.01.019. PMID 15246183.
- ↑ <ref name="RazJablons2006">Raz, Dan J.; Jablons, David M. (2006). "Bronchioloalveolar Carcinoma Is Not Associated with Younger Age at Diagnosis: An Analysis of the SEER Database". Journal of Thoracic Oncology. 1 (4): 339–343. doi:10.1016/S1556-0864(15)31592-6. ISSN 1556-0864.</r
- ↑ Jin G, Xu L, Shu Y, Tian T, Liang J, Xu Y; et al. (2009). "Common genetic variants on 5p15.33 contribute to risk of lung adenocarcinoma in a Chinese population". Carcinogenesis. 30 (6): 987–90. doi:10.1093/carcin/bgp090. PMID 19369581.
- ↑ Hsiung CA, Lan Q, Hong YC, Chen CJ, Hosgood HD, Chang IS; et al. (2010). "The 5p15.33 locus is associated with risk of lung adenocarcinoma in never-smoking females in Asia". PLoS Genet. 6 (8). doi:10.1371/journal.pgen.1001051. PMC 2916850. PMID 20700438.
- ↑ Liu YY, Chen YM, Huang MH, Perng RP (2000). "Prognosis and recurrent patterns in bronchioloalveolar carcinoma". Chest. 118 (4): 940–7. PMID 11035660.
- ↑ Sakurai H, Dobashi Y, Mizutani E, Matsubara H, Suzuki S, Takano K; et al. (2004). "Bronchioloalveolar carcinoma of the lung 3 centimeters or less in diameter: a prognostic assessment". Ann Thorac Surg. 78 (5): 1728–33. doi:10.1016/j.athoracsur.2004.05.017. PMID 15511463.
- ↑ Yoshizawa A, Motoi N, Riely GJ, Sima CS, Gerald WL, Kris MG; et al. (2011). "Impact of proposed IASLC/ATS/ERS classification of lung adenocarcinoma: prognostic subgroups and implications for further revision of staging based on analysis of 514 stage I cases". Mod Pathol. 24 (5): 653–64. doi:10.1038/modpathol.2010.232. PMID 21252858.
- ↑ Lee, K S; Kim, Y; Han, J; Ko, E J; Park, C K; Primack, S L (1997). "Bronchioloalveolar carcinoma: clinical, histopathologic, and radiologic findings". RadioGraphics. 17 (6): 1345–1357. doi:10.1148/radiographics.17.6.9397450. ISSN 0271-5333.
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