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  Table of Contents  
LETTER TO THE EDITOR
Year : 2015  |  Volume : 52  |  Issue : 4  |  Page : 555-556
 

“Low-grade adenocarcinoma of fetal lung type: In an elderly non-smoker female” with aberrant β-catenin expression


Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, New Delhi, India

Date of Web Publication10-Mar-2016

Correspondence Address:
S Pasricha
Department of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-509X.178439

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How to cite this article:
Pasricha S, Gandhi J S, Sharma A, Mehta A. “Low-grade adenocarcinoma of fetal lung type: In an elderly non-smoker female” with aberrant β-catenin expression. Indian J Cancer 2015;52:555-6

How to cite this URL:
Pasricha S, Gandhi J S, Sharma A, Mehta A. “Low-grade adenocarcinoma of fetal lung type: In an elderly non-smoker female” with aberrant β-catenin expression. Indian J Cancer [serial online] 2015 [cited 2019 Dec 15];52:555-6. Available from: http://www.indianjcancer.com/text.asp?2015/52/4/555/178439


Sir,

Low-grade adenocarcinoma of fetal lung type (L-FLAC)/well-differentiated fetal adenocarcinoma (WDFA) is a rare but distinct diagnostic entity comprising of 0.25% - 0.5% all primary lung tumors. The peak incidence is in fourth decade, with a mild female predominance, with fair prognosis and low death rate.[1],[2],[3] We report a case of L-FLAC.

A 58-years-old hypertensive non-smoker female presented with complaints of hemoptysis for 3 weeks duration. Routine lab investigations (hematological and biochemistry parameters) were normal. Computed tomography (CT)-chest revealed a lobulated soft tissue density mass lesion involving the upper lobe of right lung, measuring 51 × 41 mm [Figure 1]. No significant intra-thoracic lymphadenopathy or pleural effusion evident. Subsequently, whole body positron emission tomography (PET)-CT findings were consistent with the known mass lesion and were suggestive of malignancy. No other metabolically active foci or mass lesion evident. CT-guided FNAC was hemorrhagic and inconclusive. Patient underwent right lobectomy. Grossly, specimen measured 13 × 9 × 2 cm with peripheral nodular mass measuring 4 cm in maximum dimension. Overlying visceral pleura and bronchial cut margin were grossly free.
CT-chest showing a lobulated soft tissue density mass involving upper lobe of right lung

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Microscopic examination showed a fairly circumscribed neoplasm comprising of complex glandular architecture with tubular, papillary, and cribriform pattern admixed with scant spindle cell stroma. The glandular epithelium was columnar having ovoid bland nuclei with minimal stratification. Supranuclear and subnuclear clearing of cytoplasm was seen at places resembling secretory endometrium [Figure 2]. Mitotic activity was sparse. Solid morule formation with focal squamoid differentiation was evident. No sarcomatous area was seen. Tumor cells were positive for keratin (AE1/AE3 antibody), keratin 7, epithelial membrane antigen, beta(β)-catenin, chromogranin A, synaptophysin, and neural cell adhesion molecule (N-CAM) [Figure 3] and were negative for thyroid transcription factor (TTF-1), p63, p53, CK5, and alpha-feto protein. Stromal cells were positive for vimentin. Morules were strongly positive for Keratin, β-catenin, and weakly for chromogranin A. β-catenin expression [Figure 4]a] was aberrant nuclear/cytoplasmic (N/C). This expression pattern of β-catenin resembles that of a developing fetal lung in early weeks of gestation. At later stages of gestation, the peripheral branching airway epithelium show only membranous positivity, which was evident in the non-neoplastic lung parenchyma [Figure 4]b] in presented case.[2] Hence, a final diagnosis of L-FLAC, stage IB was rendered. This tumor characteristically occurs in fourth decade with majority (80%) associated with history of smoking. However, the presented case occurred in an elderly non-smoker female. Usually high grade (H)-FLAC is predominantly seen in the elderly.[2],[4]
Figure 2: (a) Section shows tumor with papillary architecture and solid morule (H and E; ×100). (b) Section shows tumor with a papillary architecture with cells having supranuclear and infranuclear cytoplasmic vacuoles. Squamous morule is also evident (H and E; ×200). (c) High power image showing morphology of squamous morule (H and E; ×400)

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Figure 3: (a) IHC stains with keratin (AE1/AE3) highlights the morules (center) brightly as compared to the surrounding tumor (DAB; ×200). (b) IHC stains with chromogranin A highlights weaker cytoplasmic granular staining of morules as compared to the rest of the tumor (DAB; ×200). (c) IHC stains showing positivity of tumor cells for N-CAM (DAB; ×200)

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Figure 4: (a) IHC stains with β-catenin highlights aberrant N/C staining of the tumor cells (DAB; ×200). (b) IHC stains with β-catenin showing membranous staining of the adjacent normallung parenchyma (DAB; ×200)

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Differential diagnosis comprises of papillary adenocarcinoma of lung, H-FLAC, and metastatic adenocarcinoma from endometrium. Morphological features with characteristic IHC findings and whole body PET-CT scan helped to rule out the differentials and metastatic origin. Nakatani et al.[2] have evaluated 11 cases of L-FLAC, all of which showed aberrant N/C expression of β-catenin, whereas majority of H-FLAC and conventional adenocarcinoma (CAC) of lung showed membranous expression. Their study suggested that up-regulating disturbances in the Wnt signaling pathway, including mutation of the β-catenin gene, underlie the tumorogeneis of L-FLAC while H-FLAC and CAC of lung appears to have different oncogenic pathway.

Hence, it is important to recognize this rare entity with favorable prognosis and low death rate with complete surgical excision being preferred modality of treatment.


  Acknowledgements Top


Dr. Damandeep Kaur, Senior Resident. Department Of Pathology, Rajiv Gandhi Cancer Institute and Research Centre, Sector 5, Rohini, New Delhi- 110085.

 
  References Top

1.
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.  Back to cited text no. 1
    
2.
Nagashima Y, Shimoyama K, Nakamura N, Sano J, Ogawa N, Shibagaki T, et al. Aberrant nuclear localization and gene mutation of beta-catenin in low-grade adenocarcinoma of fetal lung type: Up-regulation of the Wnt signaling pathway may be a common denominator for the development of tumors that form morules. Mod Pathol 2002;15:617-24.  Back to cited text no. 2
    
3.
Vaideeswar P, Agarwal AP. Foetal adenocarcinoma of the lung. J Postgrad Med 2004;50:75-6.  Back to cited text no. 3
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4.
Nakatani Y, Kitamura H, Inayama Y, Kamijo S, Nagashima Y, Shimoyama K, et al. Pulmonary adenocarcinomas of the fetal lung type. A clinicopathologic study indicating differences in histology, epidemiology and natural history of low-grade and high-grade forms. Am J Surg Pathol 1998;22:399-411.  Back to cited text no. 4
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]



 

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