Lung

• Lung adenomas affect a wide range of ages (2 months to 80 years), with a slight female predominance in alveolar adenoma and mucinous cystadenoma; male predominance in papillary adenoma of the lung (Hum Pathol 1999;30:158, Cancer 1980;45:1486, J Bronchology Interv Pulmonol 2013;20:52)
• In bronchial adenoma, it usually affects mostly middle to elderly age patients with median age in early 70s without any sex predilection
• Mucous gland adenoma is a very rare entity; it has no sex predilection and has a wide age range (25 - 67 years) (Am J Surg Pathol 1995;19:887)

• Lung adenomas are derived from primitive respiratory epithelium
  • BRAF, EGFR, KRAS, HRAS, ALK mutations are reported in bronchiolar adenoma / ciliated muconodular papillary tumor; BRAF is the most common mutation, with other mutually exclusive driver alterations (Pathol Int 2017;67:99, Diagn Pathol 2017;12:62, J Thorac Oncol 2016;11:261, Am J Surg Pathol 2018;42:1010)
  • Microsatellite instabilities, diploid DNA pattern and nonbalanced translocation t(10;16) have been described in alveolar adenomas (Int J Surg Pathol 2004;12:155, APMIS 2007;115:1443, Cancer Genet Cytogenet 1996;89:34)
• See Diagrams / tables

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• They may appear as solid or ground glass nodules on computed tomography (CT), with some showing cavitation or cystic spaces (Am J Surg Pathol 2015;39:753, J Thorac Imaging 2002;17:163, Am J Surg Pathol 2018;42:1010)
• Definitive diagnosis requires excision and histopathologic evaluation
• Bronchial adenoma / ciliated muconodular papillary tumor
  • Well circumscribed peripherally located nodules with papillary architecture
  • Double layered cells, basal cells (p40 and CK5/6 positive) and luminal cells (TTF1: positive in distal type and negative or focal positive in proximal type)
  • Lack of nuclear atypia and low proliferative index
  • Associated with BRAF mutation
• Alveolar adenoma
  • Multicystic mass with alveolus-like spaces
  • Cysts are lined by a single layer of type II pneumocytes with bland cytology
  • Mesenchymal stroma
• Papillary adenoma
  • Circumscribed and not capsulated
  • Papillary tumor with a single layer
  • No cytological atypia / mitosis / necrosis / complex branching architecture
  • TTF1 positive
• Mucinous cystadenoma of the lung
  • Cystic mass with mucus contents
  • Benign proliferation of mucous producing epithelial cells
• Mucous gland adenoma of the lung
  • Well circumscribed endobronchial mass
  • Acinar, tubular or papillary proliferation of cytologically bland mucous secreting cells

Contributed by Maharshi Panchal, M.D.


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• 51 year old woman with 1.1 cm bronchial adenoma in the right upper lobe (Asian J Surg 2023;46:4090)
• 52 year old woman with incidental finding of a 1.2 cm subpleural alveolar adenoma in the right upper lobe, consisting of multiple cystic spaces filled with eosinophilic granular material and lined by flattened to cuboid epithelial cells without significant atypia (Pathologica 2022;114:326)
• 66 year old nonsmoking woman with a 3.7 cm lobulated irregular papillary adenoma in the posterior basal segment of the right lower lobe of the lung (Diagn Pathol 2022;17:81)

• Bronchial adenoma is usually a well circumscribed white-gray nodule measuring 7 - 70 mm; cut surfaces can be solid, cystic or mucoid (Hum Pathol 1986;17:1066, Hum Pathol 1999;30:158, APMIS 2007;115:1443)
• Alveolar adenoma is a well circumscribed mass, which can have lobulated, multicystic pale yellow to tan cut surfaces
• Papillary adenoma may lack gross papillae or necrosis (J Bronchology Interv Pulmonol 2013;20:52, Am J Clin Pathol 1992;97:393)
  • Although size range varies from 2 to 45 mm, these are most commonly 5 - 15 mm
• Mucinous cystadenoma usually consists of a mucin filled cyst, not associated with an airway; generally, cyst walls do not have a mural nodule
• Mucous gland adenomas are well circumscribed and majority of them arise within main, lobar or segmental bronchi; the cut surface is usually tan to gray with mucoid material (Am J Surg Pathol 1995;19:887)

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Contributed by Saltanat Ualiyeva, M.D., Atreyee Basu, M.D. and Jennifer M. Boland Froemming, M.D.

Contributed by Saltanat Ualiyeva, M.D. and Atreyee Basu, M.D.

• Lung, left lower lobe, lobectomy:
  • Benign bronchiolar adenoma / ciliated muconodular papillary tumor (BA / CMPT) (see comment)
  • Size: 1.5 x 1.1 x 0.7 cm
  • Resection margins: negative for tumor
  • Comment: On histology, sections show papillary architecture and are composed of bilayered cells, luminal epithelial cells and continuous basal cells. The luminal cells consist of mucous cells and focal ciliated cells. Luminal cells are predominantly negative for TTF1 and CDX2. Immunostain for CK5/6 and p63 shows a continuous basal cell layer in the lesion. These features support the diagnosis.
  
  
• Lung, right upper lobe, biopsy:
  • Papillary neoplasm of lung, favor papillary adenoma (see comment)
  • Comment: Sections show fragments of papillae with fibrovascular cores, lined with a single layer of cuboidal epithelium without nuclear atypia, pleomorphism or prominent nucleoli. The lesional cells express TTF1 and have a low Ki67 proliferative index (< 1%). The definitive diagnosis is deferred to the complete excisional specimen.

Which features are characteristic of the entity in the image above?

1. Commonly affects children
2. Lesion has high degree of atypia and mitotic activity
3. Lesion usually has poorly defined borders
4. Proliferation of basal cell layer and luminal cells layer

D. Proliferation of basal cell layer and luminal cells layer. Bronchial adenomas are usually clinically silent well circumscribed peripherally located nodules with papillary architecture, consisting of basal cells and proliferating luminal cells. These lesions lack nuclear atypia and have a low proliferative index. Answer A is incorrect because bronchial adenomas are commonly seen in middle aged to elderly patients. Answer C is incorrect because bronchial adenomas are well circumscribed. Answer B is incorrect because bronchial adenomas are usually cytologically bland.

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Reference: Adenoma

What is the most common mutation in bronchiolar adenoma / ciliated muconodular papillary tumor?

1. ALK
2. BRAF
3. ERG
4. RB1

B. BRAF. The most common mutation in bronchial adenoma is BRAF V600E, followed by EGFR exon 19 deletions, exon 20 insertions and KRAS mutations. Answers A, C and D are incorrect because those mutations are not common in bronchial adenomas.

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Reference: Adenoma