| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Keywords: bronchioloalveolar carcinoma, BAC, history of lung carcinoma, Jaagsiekte disease
In 1876, Louis Malassez (1842–1909), a French clinical microscopist who designed the first hemocytometer, reported the first gross and microscopic description and illustration of a lung tumor [1]. The tumor was a carcinoma with distinct alveolar distribution, containing areas of fusion of tumor nodules, central necrosis, and disappearance of alveolar architecture. In 1919, James Ewing (1866–1943), Professor of Pathology at Cornell University Medical College in New York, in the first edition of his seminal book on Neoplastic Diseases [2], described an unique type of carcinoma arising from the pulmonary alveoli. He distinguished solitary and multiple nodular forms, as well as a diffuse infiltrative form. "Microscopically," he wrote, "the cuboidal, cylindrical, or flat cells partially or completely fill the alveoli and may spread through the lung by way of the air passages, interstitial septa, lymphatics, and blood vessels."
Pathologists continued to observe an alveolar lung tumor with characteristic gross and microscopic features in humans. Meanwhile, reports appeared from South Africa and Australia about a nodular and infiltrative pulmonary alveolar disease in sheep that was named Jaagsiekte disease [3,4]. Since Jaagsiekte disease was transmitted from one animal to another by direct contact, a viral etiology was suspected [4]. The gross and microscopic similarity of Jaagsiekte disease in sheep to alveolar carcinoma in humans was recognized by Bonne in 1939 [5] and confirmed by Delarue and Graham in 1949 [6].
By the late 1940s, cytology techniques for the detection of tumors had become ubiquitous and the microscopic appearance of alveolar carcinoma cells in bronchial secretions was reported by three pulmonary physicians at the Memorial Hospital for Cancer and Allied Diseases in New York, in collaboration with George Papanicolaou (1883–1962) of Cornell University Medical College [7]. In 1966, a clinical and pathologic study of 265 patients with terminal bronchiolar carcinoma was reported from the same institutions [8]. The writers called attention to the facts that the tumors occurred in upper lobes of the lung in almost 50% of cases, and that 29 of 85 female patients were non-smokers.
As clinical and laboratory experience accumulated with this unique disease in humans and animals, a dual cellular composition, including bronchiolar Clara cells and type 2 alveolar pneumocytes, was noted. With this information at hand, it was feasible to name and define the tumor. This task was performed by Averill Liebow, Professor of Pathology at Yale University School of Medicine and author of the first Armed Forces Institute of Pathology monograph on lung tumors. Liebow named the tumor "bronchioloalveolar carcinoma" (BAC) [9] and defined it as a "generally well-differentiated adenocarcinoma primary in the periphery of the lung beyond a grossly recognizable bronchus, with a tendency to spread chiefly within the confines of the lung by aerogenous and lymphatic routes, the walls of the distal air spaces often acting as supporting stroma for the neoplastic cells." Liebow continued that "to expect classic appearance of entirely intact parenchyma throughout as the sole support of BAC cells is imaginary" and "to insist that the tumor called BAC grows on the unaltered walls of alveoli without destruction (invasion) of pulmonary architecture is to add confusion." Liebow’s definition received general acceptance and was adopted by the World Health Organization (WHO) and the American Joint Committee on Cancer (AJCC).
In 1964, a retrovirus was isolated from lungs of sheep affected by Jaagsiekte disease [10] and in 1967 the retrovirus was successfully transmitted into sheep by inoculation [11]. Ultrastructurally, cytoplasmic Clara cell granules and lamellar bodies characteristic of type 2 pneumocytes were identified in tumor samples from humans and sheep [12,13]. Soon after, lamellar inclusions and surfactant were isolated from tissue culture of type 2 pneumocytes [14] and oncovirus-like particles were found in cell lines derived from BAC tumors [15].
Clinical, pathologic, and cytologic interest in BAC continued and it was noted that BAC can be seen as early as age 15 yr and may not be related to smoking [16]. BAC was one of the pulmonary neoplasms first diagnosed on smears prepared from transthoracic aspirates [17]. BAC was also one of the pulmonary neoplasms in which characteristic and suggestive cytologic features were identified by studying over 300 exfoliative and aspiration cytology specimens [18]. It became evident that the incidence of BAC was rising, particularly in women and non-smokers [19,20]; and that at stage I BAC can be treated exclusively by surgery with a 90% chance of 5-yr survival [21,22].
In the 1990s, it was shown that exogenous and endogenous type D and B retroviruses are responsible for neoplastic transformation of type 2 pneumocytes and Clara cells [23,24], suggesting that BAC is more likely than not a retrovirus-induced neoplasm. Also, in the 1990s, individual and classaction claims were entered by lung cancer victims against manufacturers of cigarettes with increased frequency. BACs, despite their well known occurrence in non-smokers and their little relationship to cigarette smoking [25], were included invariably with the pulmonary carcinomas of smokers and ex-smokers.
Pathologists generally make the diagnosis of BAC with consideration of the clinicoradiologic presentation, cytologic and histopathologic features, as well as ultrastructural and immunohistochemical findings. Nonetheless, a group of pathologists changed the definition of BAC to be based purely on examination of selected routine H&E stained histology slides. All neoplasms that showed stromal, vascular, or pleural invasion were classified as non-BACs [26]. It was defacto implied that BAC is a carcinoma in situ and that invasive BAC does not exist. Such a narrow definition ignores the basic principles of oncopathology and all that is known historically, cytologically, histologically, virologically, immunochemically, ultrastructurally, and oncologically about BAC. Lumping invasive BACs (most likely retrovirus-induced neoplasms) with other lung carcinomas (most likely smoking-induced neoplasms) potentially leads to misrepresentation and erroneous conclusions by those who deliberate the causation of BAC vs non-BAC types of pulmonary adenocarcinoma.
Since publication of the recent definition of BAC [26], it has been shown by us [27–29] and by others [30–32] that BAC, in animals and humans, is the result of epithelial cell proliferation (similar to that of all other malignant epithelial neoplasms) that progress to atypical hyperplasia, carcinoma in situ, and invasive and metastatic carcinoma if the lesion remains undetected and untreated. Invasive and metastatic BACs retain some of the microscopic features specific for BAC [28–30]. Hence, the existence of invasive and metastatic BACs cannot be denied.
While it is tempting to offer concluding remarks, I prefer to let readers reflect on the saga of BAC, as presented from its origins to the present time, and draw their own conclusions.
 |
References |
|---|
 Top References |
|---|
This article has been cited by other articles:
|
|
 |
|
  S. I. Hajdu and S. Z. Ali Discovery of Human Papillomavirus in Carcinoma of the Lung Ann. Clin. Lab. Sci., January 1, 2008; 38(1): 3 - 5. [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
