Resp. Tract

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Homme de 72 ans insuffisant rénal, tabagique, découverte radiologique fortuite d'une lésion pulmonaire.

Biopsie endobronchique négative. Lésion hypermétabolique au PET. Résection chirurgicale.

 

72 yo male with renal insufficiency, smoker, pulmonary lesion discovered on systematic checkup.

Endoscopic biopsy negative. Lesion is hypermetabolic on PET. Surgical excision.

 
     
     
     
     
       
     
       
     
         
     
     
         
     
      Alcian Blue  
     
  Bleu alcian   Alcian Blue  
 

Diagnostic proposé

 

 

 

 

 

 

 

Adénocarcinome à Prédominance Lépidique, non mucineux *

(Anciennement :Carcinome bronchiolo-alvéolaire de type non mucineux

 

Proposed diagnosis

 

 

 

 

 

 

 

Nonmucinous Lepidic Predominant Adenocarcinoma *

(Formerly: Non mucinous bronchiolo-alveolar carcinoma.)

 
 

* Multidisciplinary Classification of Lung Adenocarcinoma (click to download)

WD Travis et al. Journal of Thoracic Oncology • Volume 6, Number 2, February 2011

 
  Arguments   Clues  
     
         
  Ref Rosai and Ackerman’s Surgical Pathology (10th Ed.)  
 

Bronchioloalveolar carcinoma and related tumors.


Bronchioloalveolar carcinoma (BAC) can present grossly in various forms that bear an important relationship to its microscopic type and prognosis: a single peripheral nodule, multiple nodules, and a diffuse pneumoniclike infiltrate. The latter two forms may involve several lobes or even bebilateral. In these instances, the surgeon is often unaware that the lesion is a neoplasm. Microscopically, BACs have been divided into mucinous and nonmucinous types. They differ so much from each other as to suggest that they are two different, unrelated entities.

The mucinous type has a glistening appearance on gross examination; there is usually preservation of the underlying lung architecture, with occasional distortion of air spaces by pools of mucus.

Microscopically, the tumor is formed by well differentiated mucin containing columnar cells that line respiratory spaces in a ‘lepidic’ fashion without invading the stroma. The tumor nodules have a topographic association with bronchioles rather than bronchi. Continuity between tumor cells lining alveoli and the epithelium of respiratory bronchioles or alveolar ducts can be demonstrated. A sharp separation is often found between the neoplastic and the normal cells, a useful diagnostic feature. Rare cases have been reported of mucinous BAC with a rhabdoid component.

The reported cases of benign, borderline, and well differentiated malignant mucinous lung tumors are probably histogenetically related to the mucinous type of BAC. An increased number of cases of mucinous BAC is being reported in young patients with type 1 pulmonary congenital cystic adenomatoid malformation, suggesting that the latter may be a BAC precursor.
The differential diagnosis of mucinous BAC includes primary adenocarcinoma of the conventional type and metastatic adenocarcinoma.
Multicentric BAC can coexist with ordinary adenocarcinoma in the same lung, and an overlapping of BAC and conventional adenocarcinoma features can be seen within the same lesion. In such cases, it is important to record the presence and relative amounts of the two components. The main differences encountered between mucinous BAC and conventional adenocarcinoma are a higher incidence of multiplicity and a slightly better survival rate in the former. Most authors believe that the features of BAC are distinctive enough to warrant its separation from the other subtypes of adenocarcinoma. Interestingly, the incidence of BAC seems to be on the rise.


 
  The nonmucinous type of BAC (which comprises 60–75% of the cases) presents grossly as gray–white foci of parenchymal consolidation, sometimes
associated with a central scar.
 
 

Microscopically, the pattern of growth is again ‘lepidic’, without stromal infiltration. The tumor cells are cuboidal rather than columnar and often have a bright eosinophilic cytoplasm. The degree of nuclear atypia and nucleolar prominence is greater than in the mucinous variety. Apical sprouts may be present as indicators of Clara cell differentiation. Hobnail cells may be present. Cilia are exceptionally rare; their presence should suggest the alternative possibility of a reactive condition. Eosinophilic intranuclear inclusions, which are PAS positive, made of bundles of microfilaments ultrastructurally, and contain surfactant, are commonly seen. They represent a useful diagnostic sign, but it should be noted that intranuclear inclusions of similar or different appearances can also be seen in adenocarcinomas of the conventional types.

In contrast to the mucinous type, various degrees of interstitial fibrosis and chronic inflammatory cells (some of which are S100 protein positive) are usually present.When the fibrosis is extensive, the tumor is referred to as the sclerosing variant. Psammoma bodies are found in 13% of the cases. By definition, BACs are not invasive. Otherwise typical BACs with invasive foci measuring 0.5 cm or less have been called microinvasive adenocarcinomas or minimally invasive adenocarcinomas.


Ultrastructurally and immunohistochemically
, mucinous BAC shows differentiation toward bronchiolar goblet cells, whereas the nonmucinous types comprise cells with features of Clara cells and/or type II pneumocytes, the former predominating. At the electron microscopic level, type II pneumocytes are identified mainly because of the presence of cytoplasmic lamellar inclusion bodies. These correspond to surfactant apoprotein, which is detected immunohistochemically with the antibody PE10. α1Antitrypsin is a useful immunomarker of Clara cell differentiation. A note of caution is needed concerning the immunohistochemical profile of these tumors. Whereas nonmucinous BACs are usually CK7+/CK20–/TTF1+/ CDX2– and therefore readily distinguishable from the CK7–/CK20+/TTF1–/CDX2+, metastatic colorectal adenocarcinomas, the mucinous type of BAC are usually immunoreactive for CK20 and negative for TTF1. However, in contrast with mucinous BAC, colorectal adenocarcinomas are also positive for CDX2.

In terms of mucin production, BAC is characterized by the aberrant expression of MUC3 and MUC6, in contrast to the ordinary type of adenocarcinoma.
Exceptionally, foci of endocrine differentiation are detected in BAC.

The differential diagnosis of nonmucinous BAC includes atypical adenomatous hyperplasia and reactive type II pneumocyte hyperplasia (such as that seen in association with spontaneous pneumothorax and in individuals affected by the tuberous sclerosis syndrome). Sputum or bronchial washing cytology is almost invariably negative in cases that present as single peripheral nodules but is often positive (up to 88% of the cases) for the multinodular and pneumonic-like forms. Percutaneous fine needle aspiration has been used successfully for the detection of this tumor.

In terms of natural history, the nonmucinous type of BAC has a better prognosis than the mucinous type, particularly when solitary. It is not clear whether a small amount of stromal invasion affects prognosis.
The existence of benign counterparts of nonmucinous BAC has been postulated, and the terms papillary adenoma, pneumocyte papilloma, and alveolar adenoma have been proposed for them. In addition, some authors have postulated that socalled sclerosing hemangioma is composed of type II pneumocytes and have proposed that it be renamed pneumocytoma.