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Evolving concepts in the pathology and computed tomography imaging of lung adenocarcinoma and bronchioloalveolar carcinoma.
Travis WD, Garg K, Franklin WA, Wistuba II, Sabloff B, Noguchi M, Kakinuma R, Zakowski M, Ginsberg M, Padera R, Jacobson F, Johnson BE, Hirsch F, Brambilla E, Flieder DB, Geisinger KR, Thunnisen F, Kerr K, Yankelevitz D, Franks TJ, Galvin JR, Henderson DW, Nicholson AG, Hasleton PS, Roggli V, Tsao MS, Cappuzzo F, Vazquez M.
Department of Pathology, Memorial Sloan-Kettering Cancer Center, 1275 York Ave, New York, NY 10021, USA. [email protected]
PURPOSE: To review recent advances in pathology and computed tomography (CT) of lung adenocarcinoma and bronchioloalveolar carcinoma (BAC). METHODS: A pathology/CT review panel of pathologists and radiologists met during a November 2004 International Association for the Study of Lung Cancer/American Society of Clinical Oncology consensus workshop in New York. The purpose was to determine if existing data was sufficient to propose modification of criteria for adenocarcinoma and BAC as newly published in the 2004 WHO Classification of Lung Tumors, and to address the pathologic/radiologic concept of diffuse/multicentric BAC. RESULTS: Solitary small, peripheral BACs have an excellent prognosis. Most lung adenocarcinomas with a BAC pattern are not pure BAC, but rather adenocarcinoma, mixed subtype with invasive patterns. This applies to tumors presenting with a diffuse/multinodular as well as solitary nodule pattern. The percent of BAC versus invasive components in lung adenocarcinomas appears to be prognostically important. However, a consensus definition of "minimally invasive" BAC with a favorable prognosis could not be achieved. While recognition of a BAC component is possible, the diagnosis of BAC with exclusion of invasive adenocarcinoma cannot be made by small biopsy or cytology specimens. CONCLUSION: There is a need to work toward a mutual understanding and consensus between pathologists, clinicians, and researchers with the use of the term BAC versus adenocarcinoma. Future studies should make some attempt to quantitate these components and/or other features such as size of scar, size of invasive component, or pattern of invasion. Hopefully, this work will allow definition of a category of adenocarcinoma, mixed subtype with predominant BAC/minimal invasion and a favorable prognosis.
Publication Types:
PMID: 15886315 [PubMed - indexed for MEDLINE]
Comment in:
Prognostic significance of a histologic subtype in small adenocarcinoma of the lung: the impact of nonbronchioloalveolar carcinoma components.
Sakao Y, Miyamoto H, Sakuraba M, Oh T, Shiomi K, Sonobe S, Izumi H.
Department of General Thoracic Surgery, Juntendo University School of Medicine, Bunkyo-ku, Tokyo, Japan. [email protected]
BACKGROUND: We tried to clarify whether the histologic subtypes and the size of the solid component of an adenocarcinoma are more important predictive factors for invasiveness or prognosis than is total tumor size, even in lung adenocarcinomas that were 2 cm or smaller. METHODS: Between 1996 and December 2005, after standard surgical treatment, 82 patients were diagnosed as having adenocarcinoma with a maximum diameter of 2 cm or less. The group comprised 37 females and 45 males, with ages ranging from 41 to 80 years (median, 64). The clinicopathologic records of the patients were examined with regard to age, sex, nodal status, tumor size (largest diameter of the total tumor as well as the largest diameter without the bronchioloalveolar carcinoma [BAC] component [solid component]), serum carcinoembryonic antigen level, and histologic type. These variables were analyzed as risk factors for vascular or lymphatic invasion, lymph node metastasis, and prognosis. Histologic subtype was classified into two groups: mixed BAC (mixed adenocarcinoma with BAC) and minimal or non-BAC (tumors with little or no BAC component). RESULTS: Histologic subtype was a significant predictive factor both for invasiveness (vascular or lymph vessels) and lymph node metastasis, in both univariate and multivariate analysis. Tumor diameter was not a significant factor in either univariate or multivariate analysis (p = 0.28, 0.15, respectively). However, diameter excluding the BAC component was a significant factor for invasiveness in mixed BAC type (p = 0.035), whereas total diameter was not significant (p = 0.28). Finally, histologic subtype and lymph node metastasis were significant prognostic factors for survival in both univariate (p = 0.03, 0.05, respectively) and multivariate (p = 0.04, 0.05, respectively) analyses. The 5-year survival rate was 94.4% (94.1% for pN0) for the mixed BAC type and 71.4% (78.7% for pN0) for the minimal or non-BAC type (p = 0.009; p = 0.04 for pN0 nodes). CONCLUSIONS: Small adenocarcinomas can be classified into two categories. The first category is a minimal or non-BAC adenocarcinoma that shows aggressive biological behavior. The second category is a mixed BAC, which demonstrates less invasive or aggressive biological behavior than the minimal or non-BAC type, with the degree of invasiveness being associated with the size of the non-BAC component.
PMID: 17184664 [PubMed - indexed for MEDLINE]
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Bronchioloalveolar carcinoma and adenocarcinoma with bronchioloalveolar features presenting as ground-glass opacities on CT.
Mirtcheva RM, Vazquez M, Yankelevitz DF, Henschke CI.
Department of Radiology, New York Presbyterian Hospital-Weill Cornell Medical Center, 525 East 68th Street, New York, NY 10021, USA.
Objective: As bronchioloalveolar carcinoma (BAC) is noninvasive but, in its later stages, has a worse prognosis than adenocarcinoma with bronchioloalveolar features (ACB), early identification and differentiation is important for therapeutic and prognostic purposes. We wanted to identify features of BAC, which differentiated it from ACB when both presented as ground-glass opacities (GGOs) on CT. Materials and methods: We reviewed all pathologic specimens of patients who were diagnosed with BAC and ACB in the lung from 1991 to 1999 in our institution and whose malignancy presented as a GGO on CT. This yielded 29 patients, 15 with BAC and 14 with ACB with GGOs on CT. Both univariate frequency table and multivariate logistic regression approaches were used to analyze the CT characteristics of these GGOs (location, GGO pattern, size, shape, margin, presence and type of air bronchogram and pseudocavitation). Results: BAC most frequently had a "GGO halo" around a solid opacity, often was a GGO "mixed with consolidation" with the smallest BACs being "pure GGO." Air bronchograms were frequently present in the largest GGOs. Pseudocavitations were rare. ACB, on the other hand, most frequently presented as a GGO "mixed with consolidation," less frequently with a "GGO halo" and rarely with "superimposed lymphangitis." The air bronchograms, frequently present, were usually tortuous and ectatic. Pseudocavitation was present in about one-third of the cases. The most useful CT features of GGO in separating those due to BAC from those due to ACB were pure (uniform) ground-glass attenuation and absence of lymphangitis. Conclusion: The CT features of BAC and ACB presenting as GGO reflect the histologic descriptions of these carcinomas.
Publication Types:
PMID: 11852215 [PubMed - indexed for MEDLINE]
Micropapillary pattern: a distinct pathological marker to subclassify tumours with a significantly poor prognosis within small peripheral lung adenocarcinoma (</=20 mm) with mixed bronchioloalveolar and invasive subtypes (Noguchi's type C tumours).
Makimoto Y, Nabeshima K, Iwasaki H, Miyoshi T, Enatsu S, Shiraishi T, Iwasaki A, Shirakusa T, Kikuchi M.
Department of Pathology and Second Department of Surgery, Fukuoka University School of Medicine, Fukuoka, Japan. [email protected]
AIMS: A micropapillary pattern (MPP) in lung adenocarcinoma, characterized by papillary structures with epithelial tufts lacking a central fibrovascular core, has been reported to be a new pathological marker of poor prognosis. However, its clinicopathological and prognostic significance in small lung adenocarcinomas (</=20 mm) remains undetermined. A new histological classification of small lung adenocarcinoma proposed by Noguchi et al. has been found to be useful since it has defined surgically curable bronchioloalveolar carcinoma (BAC)-type tumours (Noguchi's type A and B) based on the absence of active fibroblastic proliferation. However, BAC-type tumours with active fibroblastic proliferation (Noguchi's type C), which is adenocarcinoma with mixed subtypes including BAC and invasive carcinoma in the new World Health Organization (WHO) classification, account for most of the small adenocarcinomas and represent a heterogeneous group ranging from minimal to overtly invasive cancer with variable prognoses. Therefore, in this study the aim was to investigate whether MPP can be an additional histological marker(s) to subclassify this heterogeneous group in small lung adenocarcinoma. METHODS AND RESULTS: One hundred and twenty-two cases of small lung adenocarcinomas (</=20 mm in maximum dimension) classified according to the new WHO classification and Noguchi's proposal were analysed with reference to the presence of MPP. Of the 122 cases, 67 (55%) were MPP-positive and 55 (45%) were MPP-negative. Lymph node metastasis and pleural invasion were significantly more frequent in the MPP-positive group: 74% and 66% in the positive group versus 26% and 34% in the negative group, respectively. The 5-year survival of the MPP-positive group was 54%, whereas that of the MPP-negative group was 81% (P=0.024). The 5-year survival rates of BAC (Noguchi's type A and B) (n=14), mixed BAC and invasive adenocarcinoma (Noguchi's type C) (n=85) and invasive adenocarcinoma (Noguchi's type D and F) (n=23) were 100%, 68% and 36%, respectively. In patients with mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours), the 5-year survival of the MPP-positive group (n=51) was 54%, significantly lower than that of the MPP-negative group (n=23) of 100% (P=0.02). CONCLUSIONS: MPP is a simple and distinct pathological marker to subclassify tumours with a significantly poor prognosis within small (</=20 mm) mixed BAC and invasive adenocarcinoma (Noguchi's type C tumours).
Publication Types:
PMID: 15910599 [PubMed - indexed for MEDLINE]
Erratum in:- J Thorac Oncol. 2006 Jun;1(5):405.
The bronchioloalveolar carcinoma and peripheral adenocarcinoma spectrum of diseases.
Garfield DH, Cadranel JL, Wislez M, Franklin WA, Hirsch FR.
Department of Medicine, University of Colorado Health Sciences Center, Aurora, Colorado 80010, USA. [email protected]
Bronchioloalveolar carcinoma (BAC) develops from terminal bronchiolar and acinar epithelia, growing along alveolar septa but without evidence of vascular or pleural involvement. A final diagnosis of BAC can only be achieved from a surgical specimen. Problematically, BAC may exhibit multifocal involvement by means of diffuse aerogenous metastatic spread, making this definition inapplicable for patients with stage IIIB to IV disease from whom only small size biopsy or cytological specimens are obtained. The recent interest and potential importance of BAC and the related peripheral adenocarcinoma (ADC), mixed subtype, is attributable to mounting evidence that some, perhaps many, of what are called peripheral ADCs have arisen from and often contain BAC. BAC, in turn, appears to arise from smaller peripheral nodules, called atypical adenomatous hyperplasia. These developments could account for part of the increase in ADCs noted in some countries, in particular, in East Asia. Interest also stems from the observation that advanced ADC, often with BAC features, are responding in surprising fashion to tyrosine kinase inhibitors. Furthermore, some of the more rapid, dramatic, and durable responses occur when specific mutations in the epidermal growth factor receptor are present. Clinical characteristics often differ from other types of non-small cell lung cancers. These include frequent female occurrence, especially in East Asians; no or less smoking history; an often indolent course; distinctive chest computed tomographic findings; frequent presentation as an asymptomatic, sometimes small, peripheral nodule(s)/mass; multifocal/synchronous primary tumors; and less frequently as pneumonic-type consolidation or diffuse, inoperable lesions, the latter two often with bronchorrhea, and with chest-only disease. Relapses also are predominantly pulmonary, perhaps related to aerogenous spread, and responsible for mortality. Lobectomy is the treatment of choice for cure, even with pneumonic consolidation, but lesser procedures such as wedge resection or segmentectomy may be considered for what might be multifocal, synchronous primary tumors and for pulmonary relapses. Because of frequent lung-only recurrences, lung transplantation, although performed rarely, may hold promise.
Publication Types:
PMID: 17409882 [PubMed - indexed for MEDLINE]
Erratum in:- Eur Radiol. 2006 May;16(5):1185.
Subtypes of peripheral adenocarcinoma of the lung: differentiation by thin-section CT.
Nakazono T, Sakao Y, Yamaguchi K, Imai S, Kumazoe H, Kudo S.
Department of Radiology, Saga Medical School, Nabeshima 5-1-1, Saga, 849-8501, Japan. [email protected]
The purpose of this study was to scrutinize morphological characteristics of thin-section CT of the histopathological subtypes of adenocarcinoma of the lung. The subjects consisted of 83 patients with 87 adenocarcinomas measuring 3 cm or less in the largest. The tumors were divided into three groups (group I: Noguchi's histological subtypes type A and B tumors, group II: type C tumors, and group III: type D, E, and F tumors). In each group, tumor size, shape (round versus polygonal), presence of air bronchogram, bubble-like areas, coarse spiculation, pleural tag, and ratio of ground glass attenuation (GGA) were evaluated. Most of the group II lesions showed polygonal shape, whereas tumors in other groups were round in shape (P<0.01). Air bronchogram and bubble-like areas of low attenuation was seen more frequently in group II compared with those in group III (P<0.01). GGA areas were largest in group I and smallest in group III (P<0.01). We believe thin-section CT findings reflect the histopathological subtypes of adenocarcinoma of the lung. The presence of air bronchogram and bubble-like areas of low attenuation areas in particular is useful to differentiate replacement growth tumors from non-replacement growth tumors.
PMID: 15846496 [PubMed - indexed for MEDLINE]
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