|Year : 2014 | Volume
| Issue : 2 | Page : 419-421
Well-differentiated fetal adenocarcinoma of the lung in an adult male: Report of an unusual tumor with a brief review of literature
Rashmi Patnayak1, Amitabh Jena2, N Rukmangadha1, AY Lakshmi3, Abha Chandra4
1 Sri Venketeswar Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
2 Department of Surgical Oncology, Sri Venketeswar Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
3 Department of Radiology, Sri Venketeswar Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
4 Department of Cardio vascular Surgery, Sri Venketeswar Institute of Medical Sciences, Tirupati, Andhra Pradesh, India
|Date of Web Publication||14-Jul-2014|
Sri Venketeswar Institute of Medical Sciences, Tirupati, Andhra Pradesh - 517 507
Source of Support: None, Conflict of Interest: None
We report a case of a well-differentiated fetal adenocarcinoma (WDFA) of the lung in a 50-year-old male smoker. The literature regarding this uncommon tumor is limited. This rare variant of adenocarcinoma is more common in females, in the third and fourth decades. Microscopically it is composed of neoplastic glands and tubules that resemble the fetal lung. Well-differentiated fetal adenocarcinoma is a low-grade malignancy and surgery is the preferred mode of therapy. This uncommon case of a well-differentiated fetal adenocarcinoma in an adult male patient is reported, with relevant immunohistochemical findings, along with a discussion of the current literature.
Keywords: Fetal adenocarcinoma, immunohistochemistry, lung
|How to cite this article:|
Patnayak R, Jena A, Rukmangadha N, Lakshmi A Y, Chandra A. Well-differentiated fetal adenocarcinoma of the lung in an adult male: Report of an unusual tumor with a brief review of literature. J Can Res Ther 2014;10:419-21
|How to cite this URL:|
Patnayak R, Jena A, Rukmangadha N, Lakshmi A Y, Chandra A. Well-differentiated fetal adenocarcinoma of the lung in an adult male: Report of an unusual tumor with a brief review of literature. J Can Res Ther [serial online] 2014 [cited 2019 Nov 21];10:419-21. Available from: http://www.cancerjournal.net/text.asp?2014/10/2/419/136677
| > Introduction|| |
Well-differentiated fetal adenocarcinoma (WDFA) is a rare pulmonary neoplasm.  Its synonyms include low-grade adenocarcinoma of the fetal lung type and pulmonary endodermal tumor resembling the fetal lung. According to the recent World Health Organization (WHO) classification, it is considered to be a variant of lung adenocarcinoma with a good prognosis.  The mesenchymal component in WDFA is benign in nature, in contrast to the biphasic pulmonary blastoma. Mortality from the WDFA is low; hence, it is important to identify this rare variant of adenocarcinoma.
| > Case report|| |
A 50-year-old male presented with a short history of chest pain, of six days' duration. It was burning pain in the retrosternal region radiating to the left arm, associated with sweating. He had shortness of breath (grade II) and one episode of hemoptysis. He was a smoker and alcoholic. He started smoking at the age of 15 years, smoking 10 cigarettes and twenty bidis per day, for the past 34 years. He was neither hypertensive nor diabetic. Hematological and biochemical investigations, sputum examination, and arterial blood gases did not reveal any abnormality. A chest X-ray and a computerized tomography (CT) scan revealed a mass lesion in the right lung [Figure 1] and [Figure 2].
|Figure 1: Chest X-ray showing a well-defined opacity in the upper and mid zone of the right lung|
Click here to view
|Figure 2: Computed tomography scan showing a well-defined lesion in the posterolateral aspect of the upper lobe, right lung|
Click here to view
The Fine Needle Aspiration Cytology finding was suggestive of neuroendocrine carcinoma. The preoperative clinical diagnosis of Bronchogenic carcinoma was considered. He underwent right upper lobectomy, with mediastinal and peribronchial lymph node sampling. The operative findings showed a spherical-shaped tumor, approximately 10 × 10 cm in size, in the posterolateral aspect of the right upper lobe abutting the oblique and horizontal fissures, without infiltrating the middle and lower lobes or parietal pleura. No pleural effusion or deposit was noted.
Gross pathological examinationof the specimen revealed a large (10 × 10 × 4 cm), well-circumscribed, yellowish lesion, with areas of necrosis [Figure 3]. Microscopically the tumor was made of glands and tubules, embedded in a bland-appearing, spindle-celled stroma. The cells lining the glands were tall, columnar, and focally stratified, with innocuous, ovoid nuclei. Many cells had supranuclear and/or subnuclear cytoplasmic vacuoles, simulating the secretory endometrium [Figure 4] and [Figure 5]. Occasional squamous morules were present. Microscopically, all margins were free and all mediastinal lymph nodes including peribronchial lymph nodes did not show evidence of metastasis. The final pathological staging was stage IIB (T3N0M0).
|Figure 3: Cut section showing a large, well-circumscribed tumor, with areas of necrosis|
Click here to view
|Figure 5: WDFA composed of glands and tubules with the lining epithelial cells showing subnuclear and supra-vacuoles resembling secretory endometrial glands (H and E, ×40)|
Click here to view
Periodic acid Schiff (PAS) staining demonstrated glycogen within the cytoplasm of the neoplastic cells. Stains for mucin were negative. Immunohistochemically the neoplastic glands showed positivity for the epithelial markers, like the epithelial membrane antigen and cytokeratin, whereas, the stroma was positive for the mesenchymal marker vimentin. Estrogen and progesterone receptors, neuron-specific enolase, chromogranin, synaptophysin, desmin, p53, and S-100 protein were all negative.
The final histopathological diagnosis was WDFA. Our patient had an uneventful postoperative recovery and was referred to the Oncology Unit, and was put on four cycles of adjuvant chemotherapy, with carboplatin and paclitaxel. He is doing well after one-and-a-half years of follow-up.
| > Discussion|| |
The term WDFA of the lung was introduced by Kodama et al., as it resembles the fetal lung of 10-15 weeks' gestational age.  WDFA, previously considered as a variation of pulmonary blastoma, is now categorized as a distinct subtype of adenocarcinoma in the recent WHO classification.  The incidence of WDFA is estimated to be only 0.5% of all pulmonary neoplasms.  This tumor is mostly described in females in the third to fourth decades, as a well-circumscribed lesion within the lung parenchyma or as endobronchial masses. , Even encapsulated tumors have been described.  WDFAs are usually smaller tumors (<5 cm), and patients are more likely to be asymptomatic. Lymphadenopathy and pleural effusion are rare in WDFA. 
Histologically the tumor is composed of neoplastic glands and tubules lined by non-ciliated columnar cells, with infra- and supranuclear vacuoles mimicking secretory endometrial glands.  These glands are rich in glycogen, as demonstrated by the PAS staining.
It is important to distinguish such tumors from metastatic endometrioid carcinoma, particularly in females, as it resembles the endometrial glands. Similar glandular patterns are also noted in pulmonary blastoma, which is more aggressive than WDFA.  Pulmonary blastoma is a biphasic tumor, which has both carcinomatous and sarcomatous components, in the form of fetal-type malignant glands and an embryonic malignant stroma.  Aberrant nuclear/cytoplasmic beta-catenin expression by upregulation of the Wnt signaling pathway has been recently described in these tumors, thereby, providing a probable pathogenetic role of this gene in WDFA. 
Well-differentiated fetal adenocarcinoma, in the absence of metastasis, following adequate surgical resections, has a better prognosis than biphasic pulmonary blastoma and other pulmonary malignancies at a similar stage. Previous studies suggest that the 10-year survival for WDFA is about 75% and for biphasic pulmonary blastoma it is about 15%. , Complete surgical resection is the preferred mode of therapy for WDFA.  In inoperable tumors or after incomplete resections, combination chemotherapy and radiotherapy can be given.
According to an extensive literature review done by Esper et al., the standard treatment for pulmonary blastoma is also surgery; however, radiotherapy and chemotherapy (usually a platinum-based regimen) have been used. In advanced inoperable tumors, radiotherapy and combined chemotherapy, consisting of cisplatin, etopside, and doxorubicin, has been shown to obtain partial remission. Patients with a biphasic tumor had a poorer prognosis compared to those with a monophasic tumor. 
Well-differentiated fetal adenocarcinoma is of low-grade malignant potential and associated with a low mortality rate, hence, it is important to identify this tumor, based on the age, gender of the patients, cytological and nuclear features of the glands, and appearance of the stroma. ,
Poor prognosis is associated with the presence of thoracic lymphadenopathy, initial metastases, and tumor recurrence.
| > Conclusion|| |
The characteristic histopathological features like typical glandular and tubular formations, with a bland cytology resembling secretory endometrial glands and benign-appearing stroma, in addition to squamous morules, helped in the diagnosis of this uncommon tumor in an elderly male, along with the clinical and imageological findings. Although in literature, this tumor is said to be present in females in the third and fourth decades, it can also be seen in adult males, as in our case.
| > References|| |
|1.||Kodama T, Shimosato Y, Watanabe S, Koide T, Naruke T, Shimase J. Six cases of well-differentiated adenocarcinoma simulating fetal lung tubules in pseudoglandular stage. Comparison with pulmonary blastoma. Am J Surg Pathol 1984;8:735-44. |
|2.||Colby TV. Adenocarcinoma. In: Travis WD, Brambilla E, Harris CC, editors. World Health Organization Classification of Tumors: Tumors of the Lung, Pleura, Thymus and Heart. Lyon: IARC Press; 2004.p. 35-44. |
|3.||Esper A, Force S, Gal A, Wolfenden LL. A 36-year-old woman with hemoptysis and a lung mass 3 months after delivery. Chest 2006;130:1620-3. |
|4.||Sheehan KM, Curran J, Kay EW, Broe P, Grace A. Well differentiated fetal adenocarcinoma of the lung in a 29 year old woman. J Clin Pathol 2003;56:478-9. |
|5.||Vaideeswar P, Agarwal AP. Foetal adenocarcinoma of the lung. J Postgrad Med 2004;50:75-6. |
|6.||Mardini G, Pai U, Chavez AM, Tomashefski JF Jr. Endobronchial adenocarcinoma with endometrioid features and prominent neuroendocrine differentiation. A variant of fetal adenocarcinoma. Cancer 1994;73:1383-9. |
|7.||Zaidi A, Zamvar V, Macbeth F, Gibbs AR, Kulatilake N, Butchart EG. Pulmonary blastoma: Medium-term results from a regional center. Ann Thorac Surg 2002;73:1572-5. |
|8.||Sekine S, Shibata T, Matsuno Y, Maeshima A, Ishii G, Sakamoto M, et al. Beta-catenin mutations in pulmonary blastomas: Association with morule formation. J Pathol 2003;200:214-21. |
|9.||Fujino S, Asada Y, Konishi T, Asakura S, Kato H, Mori A. Well-differentiated fetal adenocarcinoma of lung. Lung Cancer 1995;13:311-6. |
|10.||Sato S, Koike T, Yamato Y, Yoshiya K, Honma K, Tsukada H. Resected well-differentiated fetal pulmonary adenocarcinoma and summary of 25 cases reported in Japan. Jpn J Thorac Cardiovasc Surg 2006;54:539-42. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]