Answer: Well-differentiated Fetal Adenocarcinoma

Histology: This tumor is well circumscribed and consists of a mass of branching tubules, often with a prominent cribriform pattern. The tubules are lined by pseudostratified, nonciliated columnar cells which have a clear or lightly eosinophilic cytoplasm. Nuclei are oval or round without hyperchromasia and without pleomorphism. Often, the cells forming the tubules have subnuclear or supranuclear cytoplasmic vacuoles producing the distinctly “endometrioid” appearance. Other patterns may be cords, ribbons, solid epithelial nests, or structures resembling minute rosettes. The vast majority of cases of WDFA show morules which are solid balls of squamoid cells with ample eosinophilic cytoplasm usually found filling the glandular lumen. The tumor cells frequently show evidence of neuroendocrine differentiation and they stain positively for chromogranin or a number of polypeptide hormones, such as calcitonin, synaptophysin, somatostatin and serotonin. Some of the tumor cells will have optically clear nuclei which stain positively for biotin. The stroma of WDFA is typically scant and composed of benign spindle cells (? myofibroblasts).

Discussion: Although WDFA was originally described as Pulmonary Adenocarcinoma of Fetal Type, or Pulmonary Endodermal Tumor resembling Fetal Lung as well as Well Differentiated Fetal Adenocarcinoma, it now seems clear that this lesion actually is part of the pulmonary blastoma family of mixed epithelial and mesenchymal tumors in the lung. Except for the presence of malignant stroma, WDFA closely resembles the classic biphasic pulmonary blastoma seen in adults. Neither WDFA nor classic biphasic pulmonary blastoma resembles the pediatric lesion known as pleuropulmonary blastoma. This latter lesion is composed almost entirely of malignant stroma, with a prominent cambium layer and often with heterologous elements. As the presence of morules might suggest, the tumor cells of WDFA are positive for beta-catenin. Akatani et al (Hum Pathol 35:869-874, 2004) noted that aberrant beta-catenin expression may be a common denominator for the morular formation of tumors from various anatomic sites. They found that estrogen receptor-beta was also positive in the cytoplasm of tumor cells from this family. They suggest the terminology BRONC-family tumors for these entities. Interestingly, Sekinae et al (Journal of Pathology 200:214-221, 2003) found that both WDFA and classic biphasic pulmonary blastoma showed beta-catenin positive staining in the tumor cells. Nakatani et al. (Am J Surg Pathol 28:921-927, 2004) demonstrated beta-catenin positivity in both the cytoplasm of WDFA and in the cytoplasm and stroma of classic biphasic pulmonary blastoma, suggesting that these two lesions are clearly related. In fact, this writer has seen several cases in which one could document a transition from WDFA to classic biphasic pulmonary blastoma. From a practical standpoint beta-catenin positivity is helpful in establishing the diagnosis of WDFA and further is helpful in separating classic biphasic pulmonary blastoma from sarcomatoid carcinomas (carcinosarcoma) of the lung in which a prominent glandular pattern is present. The presence of numerous neuroendocrine cells in WDFA may lead to some confusion with carcinoid although the overall anatomic pattern and, again, beta-catenin staining should be helpful in separating these two entities. Adenocarcinomas of the lung may have focal clear cell changes, but usually some component of the more typical pulmonary adenocarcinoma are present, and beta-catenin staining would be helpful as well. Separation of WDFA from classic biphasic pulmonary blastoma is based on the presence or absence of a malignant stroma. The diagnosis of WDFA when rigorous diagnostic criteria are used appears to be good, and perhaps even better than that of classic biphasic pulmonary blastoma.

Reference(s):
– Colby TB, Koss MN, Travis WD. Tumors of the Lower Respiratory Tract, AFIP Atlas of Tumor Pathology, Third Edition, Washington, D.C., 1995.