|
Emerging approaches to advanced bronchioloalveolar
carcinoma.Curr
Treat Options Oncol. 2006 Jan;7(1):69-76.
Bronchioloalveolar carcinoma (BAC) is a subtype of non-small cell lung
adenocarcinoma that has distinct epidemiologic, histologic,
radiographic, and clinical features. The strict pathologic definition
requires an absence of any invasion through the basement membrane into
pulmonary parenchyma, but there is a growing consensus based on recent
clinical studies that this diagnosis should be considered to be based
on the clinical features of diffuse ground-glass opacities with
minimal or no extra-thoracic spread and histology demonstrating
adenocarcinoma with a lepidic growth pattern characteristic of BAC,
even if there is a component of invasive adenocarcinoma. Although
unifocal or even potentially oligometastatic disease is appropriately
treated with resection, advanced BAC is generally treated with
systemic therapy. However, multifocal BAC may be indolent enough to
follow asymptomatic patients without any systemic therapy if patients
are comfortable with this approach, because the rate of disease
progression may be slow enough to warrant no therapy for many months
or even years. For patients who have symptoms and/or clear evidence of
progression over a short interval, standard chemotherapy is
appropriate, but I would consider treatment with the epidermal growth
factor receptor (EGFR) tyrosine kinase inhibitor (TKI) erlotinib to be
the most appropriate initial therapy. This is based on the
well-documented activity of the EGFR TKIs erlotinib and gefitinib, the
latter no longer commercially available in advanced BAC. Advanced BAC
is now emerging as an area of significant research, and clinical
trials are particularly appealing considerations for such patients.
The bronchioloalveolar
carcinoma and peripheral adenocarcinoma spectrum of diseases.J
Thorac Oncol. 2006 May;1(4):344-59.
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.
Multiple
bronchioloalveolar carcinomas in acromegaly: a potential role of
insulin-like growth factor I in carcinogenesis.Lung
Cancer. 2006 Nov;54(2):247-53. Epub 2006
Aug 30
The molecular
pathogenesis of lung cancer, especially multiple and synchronous
bronchioloalveolar carcinomas (BACs), is still unknown. Here, we
report two cases of multiple BACs associated with acromegaly, and
discuss about the possible relationship between these two pathological
condition. The first patient was a 52-year-old female with a history
of Hardy's surgery for pituitary growth hormone cell adenoma 2 years
earlier. The second patient was a 57-year-old female with acromegaly
and obstructive sleep apnea syndrome. Both patients were non-smokers
and showed a high serum level of insulin-like growth factor I (IGF-I)
at the time of admission, even though the level of growth hormone had
decreased. High-resolution computed tomography (HRCT) revealed
multiple small nodules with pure ground-glass opacity (GGO) in both
lungs of the first patient and a small nodule with pure GGO in the
right lung of the second one. Partial resection for these tumors were
performed under video-assisted thoracoscopic surgery. Resected lung
specimens of the first case revealed one papillary adenocarcinoma,
seven BACs, and 11 atypical adenomatous hyperplasias (AAHs). The
second case showed two foci of BACs. Immunohistochemically, all BACs
were strongly positive for IGF-IR which is a specific receptor for IGF-I,
and all AAHs were also weakly positive for IGF-IR. Since IGF-I is
known as a potent growth factor for normal as well as cancerous cells,
it might play an important role for tumorigenesis and/or tumor
progression of BACs through its interaction with and/or upregulation
of IGF-IR. In addition, much attention should be paid to detect lung
lesions in acromegaly with high serum level of IGF-I.
Bronchioloalveolar carcinoma: a review.:
Clin Lung Cancer. 2006
Mar;7(5):313-22.
Bronchioloalveolar carcinoma (BAC) is classified as a subset of lung
adenocarcinoma but has a distinct clinical presentation, tumor
biology, response to therapy, and prognosis compared with other
subtypes of non-small-cell lung carcinoma (NSCLC). Bronchioloalveolar
carcinoma disproportionately affects women, never-smokers, and Asians
and is characterized by growth along alveolar septae without evidence
of stromal, vascular, or pleural invasion. Although pure BAC accounts
for approximately 4% of lung cancers, tumors with histologically mixed
BAC and adenocarcinoma account for > 20% of all NSCLCs, and the
incidence of BAC might be increasing. Bronchioloalveolar carcinoma
histology is most commonly found in small lesions identified
incidentally on chest radiographs or computed tomography scans and
might represent a precursor lesion to invasive adenocarcinoma. As with
other subsets of NSCLC, surgical resection is the only potentially
curative treatment. Patients with unresectable BAC are more likely to
respond to the epidermal growth factor receptor tyrosine kinase
inhibitors gefitinib and erlotinib than patients with other subtypes
of NSCLC. Stage for stage, patients with BAC have a higher rate of
long-term survival but might have an increased rate of intrathoracic
recurrence than patients with other subtypes of NSCLC.
Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type:
immunohistochemical studies and mutation analysis of the p53 gene.Pathol
Res Pract. 2006;202(10):751-6. Epub 2006
Sep 7.
Bronchioloalveolar carcinoma of mixed mucinous and nonmucinous type
fulfilling the 1999 WHO criteria is rare. Here, we report a case of
this type of tumor determined entirely by histological examinations. A
57-year-old man was incidentally found to have a demarcated 3cm mass
in his lower lobe of the right lung. The tumor was composed of tall
columnar cells containing cytoplasmic mucins, cuboidal cells without
mucins, and intermediate cell types with lepidic growth patterns.
Tumor cells were distributed within a region of 2cm in diameter, and
no stromal, vascular, or pleural invasion was observed.
Immunohistochemically, both the mucinous and nonmucinous components
were positive for cytokeratin 7, TTF-1, and E-cadherin, and negative
for cytokeratin 20, consistent with the results for nonmucinous
bronchioloalveolar carcinoma. No mutations were detected in exons 5-8
of the p53 gene. The present tumor was composed mainly of
morphologically mucinous bronchioloalveolar carcinoma, but presented
different immunohistochemical profiles of ordinary mucinous
bronchioloalveolar carcinoma. This case suggests that the mucinous
component in bronchioloalveolar carcinoma of mixed mucinous and
nonmucinous type has characters dissimilar to conventional mucinous
bronchioloalveolar carcinoma, and is probably derived from the
nonmucinous component.
Comparison of the
immunophenotypes of signet-ring cell carcinoma, solid adenocarcinoma
with mucin production, and mucinous bronchioloalveolar carcinoma of
the lung characterized by the presence of cytoplasmic mucin.
J Pathol.
2006 May;209(1):78-87.
The latest
World Health Organization (WHO) classification divides adenocarcinoma
mainly into adenocarcinoma mixed subtypes, acinar adenocarcinoma,
papillary adenocarcinoma, bronchioloalveolar carcinoma, and solid
adenocarcinoma with mucin production, and it mentions several
variants, including fetal adenocarcinoma, mucinous ("colloid")
adenocarcinoma, mucinous cystadenocarcinoma, signet-ring
adenocarcinoma, and clear cell adenocarcinoma. In general, the mucin-producing
adenocarcinoma of the lung comprises signet-ring cell carcinoma (SRCC),
solid adenocarcinoma with mucin production (SA), and mucinous
bronchioloalveolar carcinoma (m-BAC), mucinous ("colloid")
adenocarcinomas and/or mucinous cystadenocarcinoma, and mucoepidermoid
carcinoma. As SRCC, SA, and m-BAC exhibit distinct clinical features,
it is important to identify differences in their immunohistochemical
characteristics to better understand their histogenesis. In this study
we analysed SRCC, SA, m-BAC, normal lung, and foregut-related
secretory tissue for immunohistochemical differences using tissue
microarrays. SRCC and SA showed high expression of MUC1 (97.4% and
100%, respectively), cytokeratin (CK) 7 (both 100%), and thyroid
transcription factor-1 (TTF-1) (81.1% and 100%, respectively). They
also showed low expression of MUC5AC (25.5% and 21.1%, respectively)
and MUC6 (18.3% and 10.5%, respectively), whereas m-BAC showed high
expression of MUC5AC (97.5%), MUC6 (75.0%), and CK7 (94.7%), but low
expression of MUC1 (57.5%), and TTF-1 (27.5%). Hierarchical clustering
showed that the immunophenotypes of SRCC and SA belong to the same
category as alveolar lining cells, whereas m-BAC clustered onto
another branch with gastric foveolar cells and bronchial goblet cells.
These immunohistochemical findings support the results of our previous
clinicopathological analysis of SRCC of the lung showing that SRCC
occurs anatomically in the peripheral portion of the lung rather than
in the bronchial gland-bearing portion.
Bronchioloalveolar carcinoma and lung adenocarcinoma: the clinical
importance and research relevance of the 2004 World Health
Organization pathologic criteria.
J Thorac Oncol. 2006 Nov;1(9 Suppl):S13-9.
INTRODUCTION:
Advances in the pathology and computed tomography (CT) of lung
adenocarcinoma and bronchioloalveolar carcinoma (BAC) have
demonstrated important new prognostic features that have led to
changes in classification and diagnostic criteria. METHODS: The
literature and a set of cases were reviewed by a pathology/CT review
panel of pathologists and radiologists who met during a November 2004
International Association for the Study of Lung Cancer/American
Society of Clinical Oncology consensus workshop in New York. The group
addressed the question of whether sufficient data exist to modify the
2004 World Health Organization (WHO) classification of adenocarcinoma
and BAC to define a "minimally invasive" adenocarcinoma with BAC. The
problems of diffuse and/or multicentric BAC and adenocarcinoma were
evaluated. RESULTS: The clinical concept of BAC needs to be
reevaluated with careful attention to the new 2004 WHO criteria
because of the major clinical implications. Existing data indicate
that patients with solitary, small, peripheral BAC have a 100% 5-year
survival rate. The favorable prognostic impact of the restrictive
criteria for BAC is already being detected in major epidemiologic data
sets such as the Surveillance Epidemiology and End-Results registry.
Most lung adenocarcinomas, including those with a BAC component, are
invasive and consist of a mixture of histologic patterns. Therefore,
they are best classified as adenocarcinoma, mixed subtype. This
applies not only to adenocarcinomas with a solitary nodule
presentation but also to tumors with a diffuse/multinodular pattern.
The percentage of BAC versus invasive components in lung
adenocarcinomas seems to be prognostically important. However, at the
present time, a consensus definition of "minimally invasive" BAC with
a favorable prognosis was not recommended by the panel, so the
1999/2004 WHO criteria for BAC remain unchanged. In small biopsy
specimens or cytology specimens, recognition of a BAC component is
possible. However, it is not possible to exclude an invasive
component. The diagnosis of BAC requires thorough histologic sampling
of the tumor. CONCLUSION: Advances in understanding of the pathology
and CT features of BAC and adenocarcinoma have led to important
changes in diagnostic criteria and classification of BAC and
adenocarcinoma. These criteria need to be uniformly applied by
pathologists, radiologists, clinicians, and researchers. The 2004 WHO
classification of adenocarcinoma is readily applicable to research
studies, but attention needs to be placed on the relative proportion
of the adenocarcinoma subtypes. Other recently recognized prognostic
features such as size of scar, size of invasive component, or pattern
of invasion also seem to be important. More work is needed to
determine the most important prognostic pathologic features in lung
adenocarcinoma.
Misclassification of bronchioloalveolar carcinoma with cytologic
diagnosis of lung cancer.J
Thorac Oncol. 2006 Nov;1(9):943-8.
INTRODUCTION:
Cytology is commonly used to diagnose non-small cell lung cancer (NSCLC)
but is an inaccurate means of diagnosis of bronchioloalveolar
carcinoma (BAC). The aims of this study were to calculate the
sensitivity and specificity of cytologic diagnosis of BAC and to
estimate the misclassification of BAC as other subtypes of NSCLC.
METHODS: Preoperative fine-needle aspiration cytology diagnoses were
compared to histology diagnoses in 222 patients, including 51 patients
with pure or mixed BAC, who underwent lung resection for NSCLC at our
institution since 1999. RESULTS: The sensitivity and specificity of a
cytologic diagnosis of BAC were 12% and 99%, respectively. Based on
cytologic diagnosis, 63% of BAC was misclassified as adenocarcinoma,
and 18% was misclassified as undifferentiated NSCLC. In this cohort,
35% of adenocarcinomas and 12% of undifferentiated NSCLC diagnosed by
cytology had BAC histology. CONCLUSIONS: Diagnosis of NSCLC by
cytology alone results in significant misclassification of BAC, most
commonly as adenocarcinoma or undifferentiated NSCLC. Because patients
with BAC respond differently to certain treatments such as endothelial
growth factor receptor inhibitors and surgical resection of multifocal
lung cancer, misclassification of BAC may have important therapeutic
implications.
From cystic
pulmonary airway malformation, to bronchioloalveolar carcinoma and
adenocarcinoma of the lung.:
Eur Respir J. 2005 Dec;26(6):1181-7.
Bronchioloalveolar carcinoma (BAC) of the lungs is a known
morphological subtype of nonsmall cell cancer. The current study
presents several carcinogenetic theories of BAC and the possible
relationship with atypical adenomatous hyperplasia and congenital
pulmonary airway malformation (CPAM). The authors present an unusual
case of BAC developed in an area of CPAM, with subsequent progression
to metastatic adenocarcinoma (AC). The case is unique due to the
combination of: early age of presentation; neoplastic transformation
of a CPAM; unaltered course over 15 yrs; and its particular pattern of
slow morphogenesis and degeneration into an invasive AC of the lung.
The case also presents the unique features of a long-standing,
unaltered natural course of paediatric BAC towards invasive and
metastatic AC, illustrating that lack of growth over many years cannot
be entirely trusted as a criterion of benignity. In conclusion,
clinicians and pathologists need to be aware of the fact that
congenital pulmonary airway malformation so far represents the only
known pre-invasive lesion for mucinous bronchioloalveolar carcinoma.
Bronchioloalveolar carcinoma of the lung 3 centimeters or less in
diameter: a prognostic assessment.Ann
Thorac Surg. 2004;78(5):1728-33.
BACKGROUND:
Bronchioloalveolar carcinoma (BAC) of the lung is a subtype of
adenocarcinoma for which the incidence is actually rising, but the
histologic definition of BAC has been recently changed by the revised
World Health Organization (WHO) classification in 1999. The clinical
features of patients with BAC diagnosed according to the recently
revised WHO classification have not yet been clarified. In this
retrospective study, we investigated the pattern of recurrence and
survival outcome for patients with resected BAC by pathology review,
compared with those in patients who had adenocarcinoma other than BAC.
METHODS: From 1985 through 2002, 108 patients underwent surgical
resection for pulmonary adenocarcinoma 3 cm or less in diameter at the
University of Yamanashi, Japan. All of the resected specimens of these
108 patients were pathologically reviewed again to confirm the
diagnosis as BAC or adenocarcinoma other than BAC. The tumor was
defined as BAC when the adenocarcinoma lesion had a pure
bronchioloalveolar growth pattern and no evidence of stromal,
vascular, or pleural invasion according to the WHO classification
(third edition). RESULTS: Twenty-five patients (23%) had a diagnosis
of BAC, and 83 (77%) had a diagnosis of other adenocarcinoma. There
was a female predominance among both patients with BAC and those with
other adenocarcinoma. Lymph node involvement was seen for 30 lesions
(36%) of adenocarcinoma other than BAC, but not for any BAC lesions.
The median duration of follow-up after surgery was 5.1 years. There
was no recurrence in the postoperative course in patients with BAC for
a 5-year disease-free survival rate of 100%, whereas the 5-year
disease-free survival rate for other adenocarcinoma was 63.5%.
CONCLUSIONS: The patients with resected BAC, which is defined as a
noninvasive adenocarcinoma by the revised WHO classification, had an
excellent prognosis. However, these results may depend on a strictly
accurate pathology diagnosis as BAC. Limited resection might be
curative in patients with focal BAC based on evidence of pathologic
noninvasive features.
Immunohistochemical
analysis of lung carcinomas with pure or partial bronchioloalveolar
differentiation.Arch
Pathol Lab Med. 2004 Apr;128(4):406-14.
CONTEXT: In 1999,
the World Health Organization redefined bronchioloalveolar carcinomas
(BACs) as those neoplasms with only a pure lepidic growth pattern and
no invasion. OBJECTIVES: The present study examined 45 lung cancers
with a BAC component (1) to determine whether these tumors would be
classified as BACs by current World Health Organization standards, (2)
to quantitate the BAC component within these tumors, and (3) to see if
phenotypic differences exist between the so-called invasive and
noninvasive regions of these tumors. DESIGN: Retrospective review of
hematoxylin-eosin-stained slides and classification of histologic
grade, tumor subtype, and percentage of pure BAC pattern, with further
characterization by immunohistochemical staining for thyroid
transcription factor 1, cytokeratin 7, cytokeratin 20, and Ki-67
antibodies. RESULTS: Only 7 (15.6%) of the 45 tumors examined could be
classified as BAC by current strict World Health Organization
criteria. Those tumors, classified as nonmucinous and mixed, showed
similar immunohistochemical staining for cytokeratin 7, cytokeratin
20, and thyroid transcription factor 1; mucinous tumors showed
disparate staining. Significant differences in immunohistochemical
staining and tumor cell proliferation were seen for the regions of
tumors designated as lepidic, infiltrative, and leading edge and for
the regions of tumors with different histologic grades (ie, well,
moderately, and poorly differentiated). CONCLUSIONS: Nonmucinous and
mixed BACs are phenotypically similar and show identical
immunohistochemical staining patterns; mucinous tumors, on the other
hand, show disparate immunohistochemical staining. Pulmonary neoplasms
designated as adenocarcinomas with a BAC component represent a
heterogenous group with a range of cell types, differentiation,
growth, and immunophenotypes. Within an individual neoplasm, there are
regional differences in these parameters as well.
Usefulness of Cdx2
in separating mucinous bronchioloalveolar adenocarcinoma of the lung
from metastatic mucinous colorectal adenocarcinoma.Am
J Clin Pathol. 2004 Sep;122(3):421-7.
We studied the
diagnostic value of Cdx2 to distinguish mucinous bronchioloalveolar
carcinoma from mucinous colorectal adenocarcinoma metastatic to the
lung. We retrieved 92 via the hospital computer system, including 30
mucinous bronchioloalveolar carcinomas, 32 nonmucinous
bronchioloalveolar carcinomas, and 30 mucinous colorectal
adenocarcinomas metastatic to the lung. All cases were confirmed by
clinical history and surgical resection with occasional
immunohistochemical studies. Cases were stained with antibodies
against Cdx2, thyroid transcription factor-1 (TTF-1), cytokeratin (CK)
7, and CK20. Bronchioloalveolar carcinoma, mucinous type, showed
positive staining for Cdx2, TTF-1, CK7, and CK20 in 0 (0%), 5 (17%),
30 (100%), and 18 (60%) of 30 cases, respectively; nonmucinous tumors
were positive in 0 (0%), 30 (94%), 32 (100%), and 0 (0%) of 32 cases,
respectively. For colorectal adenocarcinoma, the positive staining for
Cdx-2, TTF-1, CK7, and CK20 was 29 (97%), 0 (0%), 7 (23%), and 29
(97%) of 30 cases, respectively. Our results demonstrated Cdx2 as a
sensitive and specific marker for differentiating metastatic
colorectal adenocarcinoma from mucinous bronchioloalveolar
adenocarcinoma.
Resection of
multifocal non-small cell lung cancer when the bronchioloalveolar
subtype is involved. J
Thorac Cardiovasc Surg. 2003
Nov;126(5):1597-602.
OBJECTIVE:
Bronchioloalveolar lung cancer is commonly multifocal and can also
present with other non-small cell types. The staging and treatment of
multifocal non-small cell cancer are controversial. We evaluated the
current staging of multifocal bronchioloalveolar carcinoma and the
therapeutic effectiveness of resection when this tumor type is
involved. METHODS: We reviewed our experience between 1992 and 2000
with complete pulmonary resections for bronchioloalveolar carcinoma.
Kaplan-Meier survival curves were calculated from the dates of
pulmonary resection. RESULTS: Among 73 patients with
bronchioloalveolar carcinoma, 14 patients, 7 male and 7 female with a
mean age of 65 years (51-87 years), had multifocal lesions without
lymph node metastases. Follow-up was 100% for a median of 5 years
(range 2.6-8.5 years). Tumor distribution was unilateral in 9 patients
and bilateral in 5 patients. The multifocal nature of the disease was
discovered intraoperatively in 4 patients. Nine patients had 2
lesions, 4 patients had 3 lesions, and 1 patient had innumerable
discrete foci in a single lobe. Operative mortality was 0.
Postoperatively, 10 patients were staged pIIIB or pIV on the basis of
multiple foci of similar morphology; 4 patients had some differences
in histology (implying multiple stage 1 primaries). The median
survival time to death from cancer was 14 months (141 days-5.6 years).
The overall 5-year survival after resection of multifocal
bronchioloalveolar carcinoma was 64%. Unilateral or bilateral
distribution had no impact on survival. CONCLUSIONS: The current
staging system is not prognostic for multifocal bronchioloalveolar
carcinoma without lymph node metastases. Complete resection of
multifocal non-small cell lung cancer when bronchioloalveolar
carcinoma is a component may achieve survivals similar to that of
stage I and II unifocal non-small cell lung cancer. When
bronchioloalveolar carcinoma is believed to be one of the cell types
in multifocal disease without lymph node metastases, consideration
should be given to surgical resection.
Lung
adenocarcinoma with mixed bronchioloalveolar and invasive components:
clinicopathological features, subclassification by extent of invasive
foci, and immunohistochemical characterization.
Am J Surg
Pathol. 2003 Jul;27(7):937-51.
A significant
proportion of small lung adenocarcinomas consists of two components:
bronchioloalveolar carcinoma (BAC) and invasive carcinoma. The purpose
of this study was to compare their clinicopathologic features with
those of BAC and those of invasive cancer without BAC, and to define
"early invasive" lesions based on the extent of invasive foci. We
reviewed 484 lesions of resected lung adenocarcinoma and classified
them into three groups according to tumor growth pattern: group 1 (n =
102, BAC), group 2 (n = 216, adenocarcinoma consisting of BAC and
invasive carcinoma), and group 3 (n = 166, invasive adenocarcinoma
without BAC component). Group 2 was further subdivided according to
the extent of the invasive area: group 2a (n = 54), BAC with invasive
foci <or=5 mm; group 2b (n = 162), BAC with invasive foci >5 mm. These
groups were compared with regard to their clinicopathologic features,
expression of Ki-67 and p53, and expression of laminin-5, a putative
marker for tumor invasion. The positivity rates of vascular,
lymphatic, and pleural invasion in each group were as follows: 0%, 0%,
and 0% in group 1; 5.5%, 14.8%, and 1.9% in group 2a; 45.7%, 41.4%,
and 25.9% in group 2b; and 84.9%, 61.4%, and 60.8% in group 3.
Notably, no lymph node metastasis occurred in either group 2a or group
1, but it was observed in 24.1% of group 2b and 47.0% of group 3. The
mean Ki-67 labeling index, the frequency of p53 overexpression, and
the frequency of laminin-5 overexpression increased from group 1 (11%,
4%, and 0%) to group 2a (16%, 20%, and 7%) to group 2b (24%, 41%, and
23%) to group 3 (35%, 38%, and 38%). In contrast, no clear differences
were observed when lesions were subdivided according to size. Based on
the distribution pattern of Ki-67-positive tumor cells, lesions were
classified into two groups: marginal type (63%) and nonmarginal type
(37%). The latter showed a significantly higher labeling index than
the former. Moreover, the proportion of the marginal type clearly
decreased from group 1 (85%) and group 2a (87%) to group 2b (55%) to
group 3 (19%). Group 2 lesions showed characteristics intermediate
between the BAC and invasive adenocarcinoma. According to the extent
of the invasive area, we were able to define a subgroup of mixed-type
adenocarcinomas (group 2a) that could be regarded as early invasive
cancer because they showed low rates of vascular, lymphatic, and
pleural invasion, and no nodal involvement.
Comparative
analysis of clinical features and prognostic factors in resected
bronchioloalveolar carcinoma and adenocarcinoma of the lung.Anticancer
Res. 2003 Nov-Dec;23(6D):4959-65.
BACKGROUND:
Over the past few years, clinical, radiological and pathological
classification of lung adenocarcinoma and its subtypes, particularly
bronchioloalveolar carcinoma (BAC), has radically changed. PATIENTS
AND METHODS: Out of a series of 384 non-small cell lung cancer (NSCLC)
patients, submitted to surgical resection and followed-up in our
Department from 1981 to 1999, the data of 151 adenocarcinomas (35 BAC
and 116 non-BAC) were reviewed and analyzed for prognosis. RESULTS:
BAC and non-BAC series were similar in clinical and radiographic
findings, type of resection and stage. Stage I was a dominant
favorable prognostic factor (10-year survival: 58% of BAC, 41.2% of
non-BAC), albeit associated with a significant risk of second primary
metachronous lung tumor (10-year risk: 25% of BAC, 32% of non-BAC).
Other independent prognostic factors were: absence of lymph node
involvement for BAC and stage III-IV for non-BAC. In term of
prognosis, advantages of BAC over non-BAC were fewer cases with lymph
node involvement, increased presence of "well-differentiated" cells (p
= 0.016) and lower incidence of a second primary metachronous tumor.
Moreover BAC patients with a single nodule or mass also had a higher
survival expectancy (mean survival: 77 months versus 56 for non-BAC).
An unfavorable feature was the higher incidence of diffuse or
multicentric radiological forms (p = 0.012). For both groups the
presence of multiple or satellite nodules remain a diagnostic and
surgical challenge: in BAC cases the evaluation of clonality is
recommended.
Stage I pure
bronchioloalveolar carcinoma: recurrences, survival and comparison
with adenocarcinoma of the lung. Eur
J Cardiothorac Surg. 2003
Mar;23(3):409-14.
OBJECTIVE:
Bronchioloalveolar carcinoma (BAC) is considered a subtype of
adenocarcinoma of the lung, without pleural, stromal or vascular
invasion (World Health Organization (WHO) classification). Previous
reports had demonstrated a better prognosis following surgery for
patients affected by early stage BAC than those affected by other type
of non-small cell lung cancer (NSCLC). We aim to analyse differences
between stage I peripheral nodular BAC and stage I peripheral
adenocarcinoma of the lung, METHODS: From January 1, 1993 to December
31, 1999, 1158 patients were submitted to surgical resection for NSCLC.
Out of them, 28 patients (2.4%) resulted affected by stage I
peripheral pure BAC and 80 (6.9%) by stage I peripheral adenocarcinoma.
We made a comparison between these two groups. RESULTS: The percentage
of females in BAC patients was similar to that registered in
adenocarcinoma patients (21.4 vs. 17.5%). No differences were detected
between smokers in BAC and adenocarcinoma patients (P=0.331). The
upper lobes were the most common sites of the primary tumour in both
tumour subtypes (71.4 vs. 67.5%). Relapse of disease was less frequent
in BAC than in adenocarcinoma patients (14.2 vs. 33.7%); recurrent
disease developed intrathoracic with higher frequency in BAC patients
(75 vs. 33.3%). Both 5-year disease-free and long-term survival were
significantly higher in patients affected by BAC (81 vs. 51% and 86
vs. 71%, respectively) (P<0.05); when analysis is performed by
dividing stage IA from IB tumours, BAC patients resulted to have
higher DFS (stage IA, 93 vs. 58% - P=0.044; stage IB, 61 vs. 32.5%)
and higher long-term survival (stage IA, 92 vs. 79%; stage IB, 75 vs.
56%). CONCLUSION: Patients with stage I pure BAC have significantly
longer disease-free and overall survival than those with similar stage
adenocarcinoma. Even if classified as subtype of adenocarcinoma, BAC
is characterised by clinical behaviour less aggressive than similar
stage adenocarcinoma.
Reclassification of cystic bronchioloalveolar carcinomas to
adenocarcinomas based on the revised World Health Organization
Classification of Lung and Pleural Tumours.J
Thorac Imaging. 2003 Apr;18(2):59-66.
The objective of
this study was to evaluate the radiologic-pathologic correlation of
cystic change in cases of bronchioloalveolar carcinoma (BAC) using the
1999 revised World Health Organization Classification of Lung and
Pleural Tumours. A total of 304 cases diagnosed as BAC before 1999
were reviewed retrospectively for radiologic findings of cystic change
(n = 31). Of these, 20 had adequate clinical, pathologic, and
radiologic material available for review. Patient demographics and
history; the method, location, and size of specimen biopsy; and
pathology reports were evaluated. A pulmonary pathologist reviewed the
microscopic findings to confirm the diagnosis based on the 1999 World
Health Organization criteria. Chest radiographs (n = 20) and computed
tomographic scans (n = 11) were analyzed for location, size, and
multiplicity of pulmonary nodules, masses, consolidations, or
characterization of cystic change. Associated findings of
lymphadenopathy, pleural effusion, atelectasis, and underlying lung
disease were noted. There were 10 men and 10 women (mean age, 49.3
years) who participated in the study. Eleven were symptomatic.
Pathologic review, based on the revised World Health Organization
classification, yielded the diagnosis of adenocarcinoma (n = 14);
adenocarcinoma, possible BAC (n = 4); and BAC (n = 2). Radiologically,
adenocarcinoma (n = 14) manifested as a solitary pulmonary nodule/mass
(n = 5) or consolidation (n = 6) and as multifocal mixed disease (n =
3) with solitary (n = 8) or multicystic (n = 6) change. Adenocarcinoma,
possible BAC (n = 4) manifested as multifocal and multicystic
consolidations (n = 2) or mixed disease (n = 1) and as a solitary
cystic mass (n = 1). BAC (n = 2) manifested as a cystic mass (n = 1)
and as multifocal multicystic mixed disease (n = 1). Most cases of BAC
with radiologic cystic change were reclassified as adenocarcinoma. The
radiologic features of BAC may need to be redefined in light of the
current diagnostic criteria to help identify patients with limited and
potentially curable disease.
Clinical pattern and pathologic stage but not
histologic features predict outcome for bronchioloalveolar carcinoma.Ann
Thorac Surg. 2002 Nov;74(5):1640-6; discussion 1646-7.
BACKGROUND: The
histologic criteria defining bronchioloalveolar carcinoma (BAC) were
recently revised, but it is unclear whether these criteria predict
clinical behavior. This study determined the outcome of resected BAC
in relationship to clinical and radiologic disease pattern, and
pathologic features. METHODS: Between 1989 and 2000, 100 consecutive
surgically treated patients with adenocarcinomas exhibiting various
degrees of BAC features were retrospectively studied. Histology was
reviewed; tumors were classified as pure BAC, BAC with focal invasion,
and adenocarcinoma with BAC features. Clinical and radiologic pattern
were classified as unifocal, multifocal, or pneumonic. Demographic
data, tumor stage, and outcome were recorded. Survival was analyzed by
the Kaplan-Meier method, and prognostic factors were determined by the
log-rank test. RESULTS: Patient median age was 65, and 74% of the
patients were female. Pure BAC, BAC with focal invasion, and
adenocarcinoma with BAC features occurred in 47, 21, and 32 patients,
respectively. Unifocal disease occurred in 64 patients, multifocal in
29, and pneumonic in 7. Seventy-one patients had stage I/II tumors, 22
had stage III/IV, and 7 patients had Stage X tumors. Overall 5-year
survival was 74%. There was no significant difference in survival
among the three histologic subtypes. The pneumonic pattern had
significantly worse survival compared with unifocal and multifocal
patterns. Pathologic stage predicted survival, with 5-year survivals
for I/II and III/IV of 83.7% and 59.6%, respectively. CONCLUSIONS:
Clinical pattern and pathologic stage, but not the degree of invasion
on histologic examination predict survival. Multifocal disease is
associated with excellent long-term survival after resection. The
favorable survival of stage III/IV BAC indicates that the current
staging system does not fully describe this disease in patients
undergoing resection because of its distinct tumor behavior.
Expression of
cytokeratin 20 in mucinous bronchioloalveolar carcinoma.
Hum Pathol.
2002 Sep;33(9):915-20.
Mucinous
bronchioloalveolar carcinomas (BACs) can closely mimic metastatic
adenocarcinoma to the lung both clinically and morphologically.
Several studies have demonstrated that the differential expression of
cytokeratin 7 (CK7) and cytokeratin 20 (CK20) is a valuable diagnostic
tool in differentiating primary pulmonary adenocarcinomas (PPAs)
(usually CK7 positive/CK20 negative) from metastatic colonic
adenocarcinoma (usually CK7 negative/CK20 positive). The present study
is designed to correlate the histologic subtypes of PPA with
expression of 7 and 20. A total of 113 cases of bonafide PPA were
selected and classified according to the 1999 World Health
Organization criteria as adenocarcinoma, NOS (n = 80), nonmucinous BAC
(n = 14), and mucinous BAC (n = 19). Representive sections of all the
tumors were immunohistochemically analyzed for CK7 and CK20
expression. To evaluate the diagnostic utility of CK7 and CK20
expression, 6 cases of colonic adenocarcinoma metastatic to the lung
were tested with the same antibodies and compared with mucinous BAC.
Results were expressed in a semiquantitative fashion based on the
percentage of positive tumor cells: <10%, focal; 10% to 25%, 1+; 26%
to 75%, 2+; > or =76%, 3+. All 113 PPAs exhibited strong, diffuse CK7
expression. With respect to CK20 expression, 17 of the 19 cases
(89.4%) of mucinous BAC showed moderate to strong expression of this
protein, whereas only 10 cases of conventional adenocarcinomas and 4
cases of nonmucinous BAC exhibited expression. All 6 examples of
metastatic colonic adenocarcinomas were negative for CK7 and strongly
positive for CK20. In summary, mucinous BAC is distinct from other
PPAs by virtue of its CK20 expression. Although the CK7/CK20
immunoprofile is a valuable diagnostic marker for differentiating
primary lung adenocarcinoma from metastatic colonic adenocarcinoma,
caution should be exercised when dealing with mucinous BAC.
|
