The Demise of the Term Bronchioloalveolar Carcinoma.
But now, after decades of beneficial service, the term bronchioloalveolar carcinoma has itself fallen victim to our better understanding of lung cancer. As we have over the decades come to better understand lung neoplasia and preneoplasia, bronchioloalveolar carcinoma (far from being understood as a single, specific lesion as it was originally considered) has leant its appellation to 5 clinically and pathologically distinct entities, namely, 3 nonmucinous lesions (adenocarcinoma in situ, minimally invasive adenocarcinoma, and adenocarcinoma with a prominent lepidic pattern) and 2 mucinous lesions (mucinous adenocarcinoma in situ and mucinous adenocarcinoma). Tangentially, at the most recent biennial meeting of the Pulmonary Pathology Society, discussion regarding the origin of the term lepidic (which refers to neoplastic cells growing along preexisting alveolar structures) concluded that the term is not, as is frequently stated, related to butterflies or other lepidoptera. The term, in fact, is now said to be a neologism, attributed to John George Adami. (27)
With the advancing understanding of lung adenocarcinoma and its precursors, the overly widespread and inappropriate use of the term bronchioloalveolar carcinoma became increasingly recognized, and pulmonary pathologists have acknowledged for several years that "tumors showing a pure bronchioloalveolar or 'lepidic' pattern are now best regarded as adenocarcinoma-in-situ." (28(p12)) As such, adenocarcinoma in situ, a descriptive and accurate term, has recently been formally proposed as the terminology to be used instead of bronchioloalveolar carcinoma to name pulmonary lesions that are "small (<3 cm), solitary adenocarcinomas with pure lepidic growth" (29(p382)) and for which one should expect "100% disease-specific survival if the lesion is completely resected." (29(p382)) In appropriate terminological extension, "small (<3cm), solitary adenocarcinomas with predominant lepidic growth and small foci of invasion measuring 0.5 cm or less" (29(p382)) should be termed minimally invasive adenocarcinomas.
With this new terminology come new questions, one of the most important of which is how much invasion qualifies a lesion as minimally invasive adenocarcinoma. Adenocarcinoma in situ and minimally invasive adenocarcinomas are of special interest because of their 100% and near 100% 5-year survival, respectively, if completely resected. (30) As Borczuk notes, some criteria are more straightforward than others: "Some criteria are straightforward, such as invasion of the pleura, vessels or airway walls. Once there is confluent scar or desmoplasia in association with glands, this represents invasive adenocarcinoma. If there is a pattern of growth that is a recognized pattern of invasive adenocarcinoma such as acinar, papillary, solid or micropapillary, then this is invasive as well" (31(pp54-55)) (Figure). Other criteria for diagnosis of minimal invasion are more difficult: "[G]land shapes that are not consistent with alveoli, ie angulated or small nests/glands of tumor cells," (31(p55)) as well as invasive areas that have loss of alveolar macrophages, are helpful, "but this is an inconsistent criterion in practice. Finally, there are often zones of transition from the lepidic pattern to the invasive pattern, and in the zones of transition there is often a change in nuclear grade as well as cellular morphology to a more columnar than cuboidal cell." (31(p55)) It is also important to remember that these terms must be used in their proper context. The terms adenocarcinoma in situ and minimally invasive adenocarcinoma by definition cannot be applied on limited samples such as small biopsies or cytology samples. (32)
The other major group to shed the bronchioloalveolar moniker is the invasive (invasion > 5 mm) adenocarcinomas. This group is now categorized based on the individual tumor's predominant histologic pattern, namely, predominant acinar, papillary, solid, micropapillary, or lepidic adenocarcinoma, formerly classified as mixed subtype tumors with nonmucinous bronchioloalveolar pattern. (28) The acinar pattern shows glands, round to oval in shape, in a cribriform arrangement, with tumor cells around a central lumen. A solid pattern consists of polygonal tumor cells in sheets in the absence of any of the aforementioned patterns. (33) Papillary architecture consists of columnar cells along central fibrovascular cores. Notably, the micropapillary pattern, associated with a poor prognosis and a higher rate of node metastasis, is characterized by malignant cells growing in micropapillary tufts lacking fibrovascular cores. (30) The cells can be detached, connected to alveolar walls, or both, and floating ringlike glandular structures can be seen within the alveolar spaces. The lepidic pattern of growth, with tumor cells growing along preexisting alveolar structures, is characterized by the absence of acinar, solid, papillary, or micropapillary patterns of tumor cell growth. The formerly termed mucinous bronchioloalveolar carcinoma, "characterized by very bland cells with abundant intracytoplasmic mucin, seemingly 'stuck on' to alveoli with abrupt transitions," (31(p58)) is now termed invasive mucinous adenocarcinoma and is considered an invasive adenocarcinoma rather than an in situ cancer. (34) A metastatic mucinous adenocarcinoma from a nonpulmonary primary may be seen lining preexisting alveolar walls and must be distinguished from primary pulmonary mucinous adenocarcina. (30)
Ultimately, examination of the term bronchioloalveolar carcinoma serves as a historical example of the vibrancy of a utile, descriptive term that over time, with increased medical understanding, ran its course and attained obsolescence. It also serves to highlight the potential risk with the advancement of medical understanding of a term being overused to describe too many similar (but ultimately distinct) lesions, from which a term's demise is ultimately derived. Finally, the term may serve as a reminder of the value of using language precisely. At each medical student lecture, it must be reemphasized that the term is bronchioloalveolar carcinoma. It is a linguistic mouthful, and for that reason, too, the term's demise should be respectfully mourned.
Please Note: Illustration(s) are not available due to copyright restrictions.
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Yasmeen M. Butt, MD; Timothy Craig Allen, MD, JD
Accepted for publication March 27, 2014.
From the Department of Pathology, The University of Texas Southwestern Medical Center at Dallas (Dr Butt), and the Department of Pathology, The University of Texas Medical Branch at Galveston (Dr Allen).
The authors have no relevant financial interest in the products or companies described in this article.
Reprints: Timothy Craig Allen, MD, JD, University of Texas Medical Branch, Department of Pathology, 301 University Blvd, Galveston, TX 77555 (e-mail: firstname.lastname@example.org).c
Caption: An area of adenocarcinoma in situ (upper right) and an area of invasive adenocarcinoma (lower left) (hematoxylin-eosin, original magnification 320).
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|Author:||Butt, Yasmeen M.; Allen, Timothy Craig|
|Publication:||Archives of Pathology & Laboratory Medicine|
|Date:||Aug 1, 2015|
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