Frequency in surgical specimens and morphology of atypical alveolar hyperplasia of the lung (original) (raw)
Pulmonary Atypical Adenomatous Hyperplasia: Diagnostic and Therapeutic Implications
Cureus
Lung cancer still remains one of the most common cancers throughout the world, especially in smokers. Adenocarcinoma is now the predominant histological type in many western countries. The etiology of adenocarcinoma is unknown, but evidence suggests that atypical adenomatous hyperplasia (AAH) may act as a precursor lesion. Here we present two case reports of patients diagnosed with AAH on biopsy, highlighting 1) available treatment strategies and 2) AAH's progression to adenocarcinoma. A review of AAH is warranted as little literature is currently available regarding its treatment strategies, especially in light of its role as a precursor to adenocarcinoma. In this review, we will address the following topics: 1. What is the pathophysiology of AAH? 2. What is the natural history of AAH and its risk of malignant transformation? 3. When is surgery recommended? 4. What is the role of stereotactic body radiotherapy (SBRT) in the rare patient who refuses surgery?
Coexistence of Atypical Adenomatous Hyperplasia and Hamartoma of the Lung
Atypical adenomatous hyperplasia is considered to be a preliminary lesion for pulmonary adenocarcinoma while lung hamartomas (mesenchymomas) are non-neoplastic, tumor-like malformations. A patient underwent transthoracic fine-needle aspiration biopsy for a pulmonary mass and then lingulectomy following a diagnosis of adenocarcinoma. The surgical specimen was solid and 25 mm in diameter. Microscopic investigation revealed that the mass was a hamartoma with an atypical adenomatous hyperplasia focus at the periphery. We believe that the cells leading the cancer diagnosis had come from the atypical adenomatous hyperplasia focus around the hamartoma. We presented this case as atypical adenomatous hyperplasia contains atypical epithelium and can be diagnosed as a malignancy on fine needle aspiration biopsy and the coexistence of atypical adenomatous hyperplasia and hamartoma has not been reported previously.
Lung Cancer, 2003
Background: Adenomatous hyperplasia of the peripheral lung has been suggested to be a preneoplastic lesion leading to peripherally localized lung carcinomas. The paucity of data about cellular and vascular characteristics of this lesion in comparison to normal lung prompted this investigation. Material and methods : We describe results of two investigations comprising 75 cases and 70 cases, respectively, with atypical adenomatous hyperplasia (AAH) of the lung, respectively: (a) a prospective study part with thorough analysis of surgical lung specimens (lobes and lungs) for light microscopical detection of the lesion; and (b) a retrospective study part with immuno-and lectin histochemical analysis of AAH and non-neoplastic lung parenchyma monitoring expression of growth-related markers and changes in vascularization patterns. Sections of the individual cases were examined by an imageanalyzing system including automated measurement of staining intensities and structure analysis. Results : The prospective study part revealed an incidence of AAH in 2/31 cases with squamous cell carcinoma and in 5/32 cases with adenocarcinomas. No relation to pT-or pN stages was detectable, high grade AAHs were seen to be close to the tumor lesions (B/2 cm distance) and those with low grade at greater distances. Statistically significantly increased levels of expression of anti-apoptotic bcl-2, macrophage migration inhibitory factor (MIF) capable to suppress p53 activities, heparin-binding lectin, interleukin-2, galectin-1 and of binding sites for
CT Findings of Atypical Adenomatous Hyperplasia in the Lung
Korean Journal of Radiology, 2006
The aim of this study was to analyze the computed tomographic (CT) findings of atypical adenomatous hyperplasia (AAH) in the lung. Materials and Methods: The CT findings of AAHs in eight patients were retrospectively reviewed. The CT findings of each AAH lesion were evaluated for multiplicity, location, shape, size and internal density of the lesion, the interface between the normal lung and the lesion, the internal features within the lesion and any change of the lesion on the follow-up CT scans (range: 33 to 540 days; average: 145.3 days). Results: The eight patients consisted of three men and five women (age range: 43 71 years). Six of eight patients were asymptomatic. Four of them (50%) had synchronous malignancies in the lung: adenocarcinoma of the lung (n = 3), and metastatic squamous cell carcinoma from the uterus (n = 1). We could identify and evaluate eleven AAH nodules in seven patients on the CT scans. Three patients had multiple AAHs. Seven of the 11 lesions (64%) were located in the upper lobe. All the AAHs showed a well-defined oval or round shape and pure ground-glass opacity (GGO) without any solid component (size: 3.9 3 mm to 19 17 mm; internal attenuation: 467 to 785 HU). All the AAHs showed no change of their size and internal density on the follow-up CT scans. Conclusion: Atypical adenomatous hyperplasia is often associated with malignancy. This tumor is shown on CT as persistent well-defined oval or round nodular GGOs without solid components, and it does not change on the follow-up CT.
Pathologica
Alveolar adenoma is a rare tumour of the lung. It is typically found in asymptomatic adults as a peripheral or subplerual nodule on imaging examination. Microscopically, the tumour is composed of admixture of epithelial and mesenchymal component in variable sized cystic or alveolar structures. The tumour shows a benign nature. There have been no reported recurrences or metastases. Malignant transformation of alveolar adenoma and coexisting with lung carcinoma have been rarely described. In this article, we report a case of an alveolar adenoma and coexisting atypical adenomatous hyperplasia. This case, contributing to the limited numbers of cases described to date, illustrates the importance of awareness on the possibility of alveolar adenoma being associated with lung carcinoma and its precursor lesions especially when diagnosed by small biopsy specimens.
Virchows Archiv, 1997
We used immunohistochemistry and electron microscopy to evaluate the differentiation of cells comprising atypical adenomatous hyperplasia (AAH; n = 26), early bronchioloalveolar lung carcinoma (BAC; n = 11), and overt BAC (n = 16), which are assumed to constitute a continuous spectrum of developmental steps of BAC. Surfactant apoprotein (SAP), a marker for type 2 alveolar cells, was expressed in cells from all the lesions of AAH, early BAC, and overt BAC. However, the proportion of SAP-positive cells decreased and their distribution became more heterogeneous with advancing lesion grade. Urine protein 1, which is identical to the Clara cell-specific 10 kDa protein, was expressed in 70% of overt BAC, whereas only 20% of early BAC showed weak reactivity and none of AAH lesions showed any reactivity at all. Ultrastructurally, type 2 alveolar cell differentiation was predominant among cells from AAH and early BAC. Our results suggest that precursor cells of BAC differentiate predominantly towards type 2 alveolar cells. Cells comprising overt BAC retain this differentiation phenotype, but to a reduced extent. In contrast, concomitantly with progression, cells with Clara cell differentiation emerge and their proportion increases. Such phenotypic changes may reflect metaplasia occurring in tumour cells during the development of BAC.
Current status of small peripheral adenocarcinomas of the lung and their importance to pathologists
Annals of Diagnostic Pathology, 2005
There has been a large amount of work done recently on small peripheral stage I adenocarcinomas that come to resection. Radiological (including proportion of ground glass opacity) and pathological features of these lesions (predominant bronchioloalveolar component, central scar with or without invasion b 0.5 cm) have been shown to be prognostically favorable with cure rate approaching 100% in some series. Most of these studies emanate from Japan. The relevance of these studies to other parts of the world, particularly North America, is discussed in light of the fact that some recent chemotherapeutic studies with gefitinib have shown increased response in individuals of Asian origin, suggesting that some genetic differences may be significant. The relevance of these findings to pathologists and the pathological study of small peripheral adenocarcinomas from elsewhere in the world are discussed. D 2005 Elsevier Inc. All rights reserved.
Romanian journal of morphology and embryology = Revue roumaine de morphologie et embryologie, 2005
The frequency of preneoplastic lesions of the lung and bronchial mucosa as well as potential genotype alterations in spatial relationship to pulmonary malignancies still need intensive investigations in order to understand the occurrence and manifestation of lung cancer in detail. To investigate the contemporary manifestation of lung cancer precursor lesions, peripheral (non-neoplastic) lung parenchyma and bronchial mucosa of operated lung carcinomas were analyzed at distinct distances (1, 2, 3, and 4 cm) from the tumor boundary for pre-neoplastic lesions--atypical adenomatoid hyperplasia (AAH) and squamous cell dysplasia (SCD), in 150 surgical specimens. Short-term tissue cultures of additional 55 primary and secondary lung tumors and their surrounding non-neoplastic bronchial mucosa were performed at the same distances in order to search for chromosome alterations, i.e. genotype aberrations. In phenotype observations, atypical adenomatoid hyperplasia was noted in 19/150 (13%) case...
The significance of associated pre-invasive lesions in patients resected for primary lung neoplasms1
European Journal of Cardio-Thoracic Surgery, 2004
Objective: To evaluate the prevalence and clinico/prognostic significance of the presence of pre-invasive lesions in patients resected for primary lung neoplasm. Methods: From 1993 to 2002, 1090 patients received resection for primary lung carcinomas. Of these, 73 presented an associated pre-invasive lesion in the surgical specimen distant from the primary tumour. Classification of pre-invasive lesions included Atypical Adenomatous Hyperplasia (AAH); Carcinoma In Situ (CIS) either diffuse or at the bronchial resection margin; Diffuse Idiopathic Pulmonary Neuroendocrine Cell Hyperplasia (DIPNECH). Correlation between the presence of pre-invasive lesion and the following variables were calculated by logistic regression analysis: sex, age, median tumour size, histology, histologic differentiation, histologic evidence of invasiveness (vascular and perineural invasion), peritumoural lymphocytic infiltrate, pTNM, lobe location, history of previous malignancy. Survival rates were computed using Kaplan-Meier method and survival differences with the total patient population of resected lung carcinomas were tested using the log-rank method. Results: There were 28 AAH, 42 CIS (5 at the bronchial resection margin) and 3 DIPNECH. Histology of the primary tumor included bronchioloalveolar carcinoma (9 patients), adenocarcinoma (19), squamous cell carcinoma (39), typical carcinoid tumour (3) and adenosquamous carcinoma (3). Overall prevalence of pre-invasive lesion was 6.7%. A strong correlation was found between the presence of AAH and the co-existence of either adenocarcinoma, bronchioloalveolar carcinoma or mixed adenocarcinoma-containing tumours ðP ¼ 0:00002Þ; between CIS and squamous cell carcinoma ðP ¼ 0:009Þ and between DIPNECH and carcinoid tumours ðP ¼ 0:0001Þ: No significant correlation was found between the presence of any type of pre-invasive lesion and sex, age, median tumour size, histologic differentiation, histologic evidence of invasiveness, pTNM, lobe location and history of previous malignancy or the probability to develop a second primary lung carcinoma in the remaining lobe(s) after resection. Survival rates in the patients with AAH and CIS were not significantly different from those of patients without pre-invasive lesion (P ¼ 0:3 and P ¼ 0:1). Conclusions: Associated pre-invasive lesions in patients resected for primary lung neoplasms are not infrequent. AAH is associated with adenocarcinoma, CIS with squamous cell carcinoma, DIPNECH with typical carcinoid tumours. Our experience indicates that in these patients histology, stage distribution and survival do not differ from the total population of resected patients with lung tumors. q 2004 Elsevier B.V. All rights reserved.
Experimental and Therapeutic Medicine, 2012
The biological and chronological evolution of lung cancer remain to be fully elucidated. A multi-step carcinogenesis hypothesis suggests a progression from atypical adenomatous hyperplasia (AAH) through bronchioalveolar carcinoma (BAC) to invasive adenocarcinoma (AC), but to date this has not been formally demonstrated. We report a case of a patient diagnosed by computed tomography (CT) with lung cancer in the superior right lobe who also presented with a pure ground-glass opacity (GGO) in the inferior lobe, while the middle lobe appeared normal. Following pneumonectomy, cytogenetic analysis successfully performed on spontaneous metaphases obtained by the direct method from samples of the three lung lobes showed the presence of three clonal cell populations, each progressively having increased karyotype complexity. Fluorescence in situ hybridization (FISH), performed using ALK (2p23) break probe and ALK/ EML4 t(2;2);inv(2) fusion probe, showed a normal pattern for all specimens. Histological evaluation confirmed the presence of AC in the superior right lobe and classified the GGO lesion as BAC and the normal tissue of the middle lobe as AAH. To the best of our knowledge, this is the first case in which the cytogenetic study of spontaneous metaphases showed a clear clonal relationship among AC, BAC and AAH present simultaneously in different lobes of the same lung. This case appears to indicate that the entire lung was somehow predisposed to a neoplastic transformation starting with a diffuse AAH characterized by high proliferative activity. Moreover, the 5q13 region involved in the translocation shared by BAC and AC contains at least 4 genes encoding important regulators of the cell cycle that may be considered new molecular markers of lung cancer.
Journal of Cancer Research and Clinical Oncology, 1987
The reaction patterns in 80 adenocarcinomas of the lung were examined with P A P-m e t h o d using a m o n o c l o n a l a n t i b o d y against keratin a n d one against c a r c i n o e m b r y o n i c antigen (CEA) a n d a polyclonal a n t i s e r u m against CEA. A l m o s t all tumors showed a positive reaction to the antibodies which, however, varied quantitatively. Even t h o u g h a reliable correlation of positive i m m u n o h i s t o c h e m i c a l reaction with the different light microscopical types was n o t possible according to W H O subtypes a n d degrees of differentiation, specific localization of the reaction within the t u m o r cells was seen with increasing differentiation. There was no correlation between the i m m u n o h i s t o c h e m i c a l reactions a n d 14 clinically measured plasma C E A levels. The plasma C E A level n o t only depends o n C E A p r o d u c t i o n by the t u m o r b u t also on other factors.
Histologic features are important prognostic indicators in early stages lung adenocarcinomas
Modern Pathology, 2007
This study attempts to evaluate the clinicopathologic features of mixed subtype adenocarcinomas and the prognostic implications of histopathology classifications. Surgical specimens from 141 patients with clinical stage I or II lung adenocarcinoma during the period 1992-2004 were included. These cases were classified into four groups defined by the extent of the bronchioloalveolar carcinoma component: group I: pure bronchioloalveolar carcinoma; group II: mixed subtype with predominant bronchioloalveolar carcinoma component and r5 mm invasive component; group III: mixed subtype with bronchioloalveolar carcinoma component and 45 mm invasive component; group IV: invasive carcinoma with no bronchioloalveolar carcinoma component. Descriptive statistics were used to examine the groups with respect to age, tumor size, lymph node metastasis, and Ki-67 and p53 expression levels. Death rate for the groups was obtained by patient's charts and from the National Death Index database. The population was similar in age, tumor size and lymph node metastasis. Immunohistochemical results showed that the mean Ki-67 labeling and the amount of p53 overexpression had the same trend of increasing mean values or positive results from groups I to IV. The reported proportion of deaths ranged from 0% for groups I and II, 20% in patients with predominant invasive component with bronchioloalveolar carcinoma (group III), and 18% in patients with invasive carcinomas and no bronchioloalveolar carcinoma component (group IV). The difference between the proportion of patients with reported deaths in the time period of this study in the combined greater than 5 mm þ pure invasive groups (groups III, IV), and the o5 mm þ noninvasive groups (groups I, II) is statistically significant. These results suggest that histological features may be useful in defining categories of lung adenocarcinomas with differing survival and prognostic features. These results are helpful in defining a subcategory of 'minimally invasive adenocarcinoma', which has features similar to bronchioloalveolar carcinoma. Prognosis of small pulmonary adenocarcinoma J Yim et al Prognosis of small pulmonary adenocarcinoma J Yim et al Prognosis of small pulmonary adenocarcinoma J Yim et al
An Unusual Presentation of Aggressive Primary Invasive Adenocarcinoma of Lung
C68. THORACIC ONCOLOGY CASE REPORTS II, 2020
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Prognostic significance of percentage of bronchioloalveolar pattern in adenocarcinomas of the lung
Annals of Diagnostic Pathology, 2001
of the lung is considered to have a better prognosis than that of common adenocarcinomas of the lung. However, a minor component of the BA pattern is common in many lung adenocarcinomas and the criteria for designating an adenocarcinoma as BA are not well defined. We assessed the clinicopathologic features of 238 cases of lung adenocarcinoma with a partial or predominant BA pattern. Tumors were classified as BA if more than 75% of the tumor had a BA growth pattern. In other words, the tumor grew along pre-existing lung structures without invasion or destruction of parenchyma. Tumors with 50% to 75% BA pattern were considered mixed and tumors with less than 50% BA pattern were designated as solid/acinar (S/A). Fixed, paraffin-embedded tissue sections of each neoplasm were also assessed using immunohistochemical methods with a panel of antibodies specific for p53, retinoblastoma protein, p16, cyclin D1, and cyclin E, and the results were correlated with clinical and pathologic parameters. Our results show that the 5-year survival rate of patients with BA and mixed tumors, 63% and 60%, respectively, was significantly better than that of patients with S/A tumors (P ؍ .026). Patients with BA tumors were more frequently women (55.9%) compared with patients with mixed (48.3%) and S/A (43.8%) tumors. Bronchioloalveolar and mixed tumors were similarly associated with tobacco use, 88.2% and 85%, respectively; slightly less than S/A tumors (93.8%). Clinical and pathologic parameters did not correlate with immunohistochemical results. In conclusion, patients with BA or mixed tumors have similar 5-year survival, better than that of patients with S/A tumors, suggesting that adenocarcinomas can be designated as BA when at least 50% of the tumor has a BA pattern.
A Pattern of Carcinoma of Lung as Seen in a Tertiary Care Hospital
Biomedica, 2008
This cross sectional descriptive study was conducted to assess clinicopathological characteristics of lung cancer in 142 patients, 116 males and 26 females, from various regions of Punjab presenting with clinical features consistent with the diagnosis of lung carcinoma. They were admitted to Gulab Devi Chest Hospital (GDCH), Lahore, Pakistan from January 2005 to January 2007. Our observations revealed that the most prevalent malignancy among these patients was non small cell lung carcinoma including squamous cell carcinoma and adenocarcinoma in males and females respectively. Most common affected age groups were between 41-60 years (n=82) and 51-70 years (n=15) in males and females respectively. Squamous cell carcinoma followed by small cell lung carcinoma were commonly associated with smoking in both genders. Immunohistochemistry was employed for the confirmation of diagnoses in some (n=35) cases. We observed that 4 of 10 (40%) large cell lung carcinomas were strongly positive with HDC. The remaining 06 (60%) large cell lung carcinomas though negative for HDC, were strongly positive with Cyfra 21-1. All small cell lung carcinomas, atypical and typical carcinoids were also strongly reactive to HDC immunostaining. Antimucin antibody was also strongly positive and negative in each 02 of the 04 (50%) poorly differentiated adenocarcinomas where all of them were strongly reactive to Cyfra 21-1. It is concluded that lung cancer is more common in males and is strongly associated with smoking. Hence, interventional measures for prevention and early but correct diagnosis of bronchogenic carcinoma is needed. The role of tumour markers can be very useful in finalizing cases which are difficult to be differentiated.
Journal of Medical Case Reports, 2011
Introduction Alveolar adenomas are extremely rare, benign, primary lung tumors of unknown histogenesis that are characterized by proliferative type II alveolar epithelium and septal mesenchyma. Mostly incidental, they are clinically important as they can imitate benign primary and secondary malignant tumors and at times are difficult to differentiate from early-stage lung cancer. We describe the case of a 59-year-old man with an incidental microscopic alveolar adenoma coexisting with poorly differentiated lung carcinoma. Case presentation A 59-year-old Caucasian man with a medical history of smoking and chronic obstructive pulmonary disease was incidentally found to have a right upper lobe mass while undergoing a computed tomographic chest scan as part of a chronic obstructive pulmonary disease clinical trial. Our patient underwent a right upper lobectomy after a bronchoscopic biopsy of the mass revealed the mass to be a carcinoma. A pathological examination revealed an incidental, small, 0.2 cm, well circumscribed lesion on the staple line margin of the lobectomy in addition to the carcinoma. Histopathological and immunohistochemical examinations revealed the lesion to be an alveolar adenoma. Conclusions We report the rare presentation of a microscopic alveolar adenoma coexisting with lung carcinoma. Alveolar adenoma is an entirely benign incidental neoplasm that can be precisely diagnosed using immunohistochemical analysis in addition to its unique histopathological characteristics.
Lung Cancer, 2007
Atypical adenomatous hyperplasia (AAH) has been recently defined by WHO as a small lesion, not exceeding 5 mm in major axis, composed of slightly enlarged alveolar septa lined by pneumocytes with plump, atypical nuclei. AAH is frequently found in tissue surrounding lung adenocarcinoma and is considered a precursor of this subtype of lung cancer by many Authors. However, the genetic relationship between adenocarcinoma and the associated foci of AAH is not well defined. In particular, it is not clear whether multiple foci of AAH and of adenocarcinoma in the same patients are clonally related to each other or represent independent neoplastic foci.