Atypical goblet cell hyperplasia in congenital cystic adenomatoid malformation as a possible preneoplasia for pulmonary adenocarcinoma in childhood: a genetic analysis

Stacher, Elvira; Ullmann, Reinhard; Halbwedl, Iris; Gogg-Kammerer, Margit; Boccon‐Gibod, Liliane; Nicholson, Andrew G.; Sheppard, Mary N.; Carvalho, Lina; Franca, Maria Teresa; MacSweeney, Fergus; Morresi‐Hauf, Alicia; Popper, Helmut

doi:10.1016/j.humpath.2004.01.008

Cited by 88 publications

(60 citation statements)

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“…[14][15][16][17] In the current study, we found 24 cases of adenocarcinoma displaying transition foci from the normal ciliated columnar cell to mucous columnar cell metaplasia, dysplasia, adenocarcinoma in situ, and finally invasive adenocarcinoma. Transition foci of normal ciliated columnar epithelium to mucous columnar cell were observed in bronchiole or honeycomb spaces.…”

Section: Discussionmentioning

confidence: 97%

“…[14][15][16][17] Mucous or goblet cell proliferation has been observed in or around congenital cystic adenomatoid malformation, and those mucous columnar cells have genetic abnormalities such as loss of heterozygosity at P16 INK4 or gain/loss of chromosomes, in contrast to relatively normal lungs. 15 On the basis of our recent experience of an adenocarcinoma that displayed an extensive transition from normal ciliated columnar cell to mucous columnar cells, indicative of a spectrum from dysplastic to malignant morphology, we were compelled to consider the possibility that mucous columnar cell metaplasia and dysplasia is another obvious pathway of pulmonary adenocarcinoma. Because mucous columnar cell metaplasia arises in the bronchus or bronchiole, it seems reasonable to think that adenocarcinoma arising through mucous columnar cell change belongs to the so-called central adenocarcinoma or non-terminal respiratory unit type adenocarcinoma, and not to the terminal respiratory unit type adenocarcinoma or peripheral adenocarcinoma.…”

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confidence: 99%

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Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin

et al. 2012

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Whereas most carcinomas occur through a sequential step, atypical adenomatous hyperplasia and bronchioloalveolar carcinoma pathway is known for pulmonary adenocarcinoma. This type is known as terminal respiratory unit adenocarcinoma. Based on our observation of transitions from normal ciliated columnar cells to adenocarcinoma via dysplastic mucous columnar cells, we reviewed our archive of pulmonary adenocarcinoma. Terminal respiratory unit type adenocarcinoma was defined as adenocarcinoma with type II pneumocyte, Clara cell, or bronchiolar cell morphology according to previous reports. Among 157 cases, 121 cases have been identified as terminal respiratory unit type adenocarcinoma and 36 cases as non-terminal respiratory unit type adenocarcinoma. Among non-terminal respiratory unit type adenocarcinoma, 24 cases revealed mucous columnar cell changes that were continuous with bronchial ciliated columnar cells. The mucous columnar cells became dysplastic showing loss of cilia, disorientation, and enlarged nuclei. Adenocarcinoma arose from these dysplastic mucous columnar cells and, characteristically, this type of adenocarcinoma showed acute inflammation, and honeycombing changes in the background. TTF1 immunostaining was consistently negative. In a case study with 14 males and 10 females, including 12 smokers or ex-smokers, EGFR and KRAS mutations were detected in 3 and 6 patients, respectively. We think that this kind of adenocarcinoma arising through mucous columnar cell change belongs to non-terminal respiratory unit type adenocarcinoma, and mucous columnar cell change is a precursor lesion of pulmonary adenocarcinoma. Keywords: adenocarcinoma; lung; mucous columnar cell change Most carcinomas, including squamous cell carcinoma in the head and neck, uterine cervix, and skin, and adenocarcinomas in sites including the gastrointestinal tract, biliary tract, breast, and prostate occur through a sequence of steps from normal epithelium to hyperplasia, dysplasia, carcinoma in situ, and invasive carcinoma. 1 In the lung, squamous carcinoma arises by a similar pathway, beginning from squamous metaplasia in bronchus or bronchiole that is caused by various irritants. 2 Adenocarcinoma is considered to develop by a pathway of atypical adenomatous hyperplasia and bronchioloalveolar carcinoma. 2-4 However, whether atypical adenomatous hyperplasia-bronchioloalveolar carcinoma pathway is really the only pathway for pulmonary adenocarcinoma has been questioned on the basis of a number of observations. 5 First, atypical adenomatous hyperplasias are not as common as adenocarcinomas with features of bronchioloalveolar carcinoma or premalignant lesions in other organs. 3,5 Second, atypical adenomatous hyperplasia is morphologically different from pre-adenocarcinoma lesions in other organs such as adenoma, prostatic intraepithelial neoplasia, or biliary intraepithelial neoplasia showing nuclear stratification, elongation, and overlap. Third, peripheral pulmonary parenchyma in which atypical adenomatous hyperplasia or bronchioloalv...

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Section: Discussionmentioning

confidence: 97%

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confidence: 99%

Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin

et al. 2012

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“…rhabdomyosarcoma in children [27][28][29][30] and mucinous BAC (mostly in adults) [31][32][33][34][35][36][37][38][39][40]. These associations have been significantly underappreciated and it is unlikely that they represent random associations or publication bias.…”

Section: From Cpam To Bac and Acmentioning

confidence: 99%

From cystic pulmonary airway malformation, to bronchioloalveolar carcinoma and adenocarcinoma of the lung

Ioachimescu

Mehta²

2005

Eur Respir J

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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.KEYWORDS: Adenocarcinoma, atypical adenomatous hyperplasia, bronchioloalveolar carcinoma, carcinogenesis, congenital pulmonary airway malformation, cystic adenomatoid malformation CASE HISTORY A 6-yr-old male presented in 1988 with recurrent episodes of fever, left-sided pleuritic chest pain, cough with significant bronchorrhea, intermittent haemoptysis, fatigue, anorexia and weight loss. He was diagnosed with left lower lobe pneumonia and treated with antibiotics three times over a period of 7 months. During the last episode, the chest radiograph showed an infiltrate and airfluid level in the left lower lobe. He was hospitalised and started on antibiotic therapy. He had a negative tuberculin test, fungal serologies and bronchoalveolar lavage cultures for bacteria, acid-fast bacilli and fungi. A thoracotomy with left-lower lobe lobectomy was performed; macroscopically, the lesion resembled a pneumonic process or a congenital malformation (intra-lobar sequestration with a large secondary abscess versus a congenital cystic malformation). Microscopic examination of the resected lung revealed multicentric mucinous-type bronchioloalveolar carcinoma (BAC) developed in an area of congenital adenomatoid malformation (CAM), or congenital pulmonary airway malformation (CPAM) type I, without pleural involvement. No abscesses were found. Synchronous nodules in the right upper, middle, lower and left-lower lobes were present and surgically explored. A right-middle lobe wedge resection biopsy revealed similar lesions of BAC. Chemotherapy was offered, but in light of poor predicted prognosis, the patient's family refused any therapeutic modality.During the follow-up, the patient had intermittent chest pains, but no other symptoms. He finished school with good grades, smoked cigarettes infrequently and continued to live an active life for the following 15 yrs. Follow-up chest radiographs and computed tomography (CT...

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“…In 1998, Ota et al [17], having previously noted gastric mucins in mucinous BAC, studied 12 out of 26 cases of CPAM type 1 containing mucous cells and found mucins similar to those of the mucinous BACs. This association has been supported by the finding of similar genetic abnormalities (including gains in chromosomes 2 and 4) in both CPAM type 1 goblet cells and the cells of BAC [18]. Most recently, Ioachimescu and Mehta [14] described the 15-yr course of the development of a BAC (diagnosis at age 6 yrs, along with CPAM type 1), which subsequently developed into an invasive adenocarcinoma.…”

Section: Does Cpam Type 1 With Mucinous Foci Predispose To Bac?mentioning

confidence: 85%

Cystic lesions of the lung in children: classification and controversies

Stocker¹,

Husain²

2007

Pathology of the Lung

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Atypical goblet cell hyperplasia in congenital cystic adenomatoid malformation as a possible preneoplasia for pulmonary adenocarcinoma in childhood: a genetic analysis

Cited by 88 publications

References 13 publications

Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin

Ciliated adenocarcinomas of the lung: a tumor of non-terminal respiratory unit origin

From cystic pulmonary airway malformation, to bronchioloalveolar carcinoma and adenocarcinoma of the lung

Cystic lesions of the lung in children: classification and controversies

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