Alveolar Adenoma: A Rare Benign Tumour of the Lung with A Challenging Diagnosis
Soumaya GRAJA1, Saadia MAKNI1, Abdessalem HENTATI2, Chiraz CHAARI1, Tahya SELLAMI-BOUDAWARA1, Rim KALLEL1
1Department of Pathology, Habib Bourguiba University Hospital, SFAX, TUNISIA
2Department of Cardiothoracic Surgery, Habib Bourguiba University Hospital, SFAX, TUNISIA
Keywords: Lung tumour, Alveolar adenoma, Immunohistochemistry, Differential diagnosis
Alveolar adenoma is a rare lung benign tumour originating from type II pneumocytes. It presents as a well-defined nodule. In some cases,
it is difficult to differentiate from lung cancer. Few cases of this tumour have been reported. We describe here a case of alveolar adenoma in
a 63-year-old man discovered incidentally on chest X-ray. The lesion was reported as lepidic adenocarcinoma in bronchoscopic biopsy. The
patient underwent a thoracoscopic left lower lobectomy. The histopathological and immunohistochemical examinations resulted in a diagnosis
of alveolar adenoma. We report this case to describe its morphological and immunohistochemical characteristics and to emphasize its diagnostic
Alveolar adenoma (AA) is a rare lung neoplasm, accounting
for less than 1% of all lung tumours. It represents one of
several types of pulmonary adenomas recognized by the
revised World Health Organization classification of lung
. There are only forty cases reported in the
English medical literature.
It has a particular histology and it consists of multi-cystic
spaces lined by an alveolar epithelium overlying a spindle
cell rich stroma 2. It is typically more common in middleaged
women and presents as an asymptomatic mass found
in chest radiographs 3. The purpose of this report is to
describe a rare example of AA, and to discuss the differential
diagnosis with bibliographical considerations.
A 63-year-old man, without a significant past medical
history, presented with a solitary pulmonary nodule
located in the left lower lobe of the lung with a diameter
of 33 mm that was incidentally discovered on chest X-ray
imaging (Figure 1A
). Bronchoscopic biopsy of the mass
was performed and the microscopic examination suggested
a lepidic adenocarcinoma. The patient underwent a
thoracoscopic lobectomy. Macroscopic examination
revealed a well-circumscribed encapsulated peripheral
tumor measuring 4×3,3×2,8 cm. The cut surface was greywhite
with a spongy appearance (Figure 2
Click Here to Zoom
|Figure 1: Chest X-ray (A)
and CT scan (B) present a
33 mm, well-circumscribed,
solitary nodule in the left
Click Here to Zoom
|Figure 2: Macroscopic view of the mass: a well-circumscribed
encapsulated tumor with spongy appearance and grey-white cut
Histologically, the tumor was a multicystic mass easily
distinguished from the surrounding lung parenchyma
(Figure 3). The cystic spaces were variable in size and
were lined with thin cuboidal alveolar epithelium with
bland cytology, and they were focally filled with granular
eosinophilic material (Figure 4). The mid-alveolar septa
were flattened with microvessels and few spindle-shaped
cells, with local mild chronic inflammation. No cellular
atypia, necrosis, invasion of adjacent parenchyma, or
vascular invasion was seen. The adjacent lung tissue was
Click Here to Zoom
|Figure 3: Multi-cystic lesion with ectatic spaces filled with
eosinophilic granular material (H&E, 50x).
Click Here to Zoom
|Figure 4: The cystic spaces are variable in size, and are lined with
thin cuboidal alveolar epithelium (H&E, 100x).
In the immunohistochemical analysis, the epithelial
cells lining the spaces were diffusely positive for thyroid
transcription factor-1 (TTF-1), and cytokeratin (CK); but
were negative for clusters of differentiation 31 (CD31), and
34 (CD34) (Figure 5A-D). The Ki-67 proliferation index
Click Here to Zoom
|Figure 5: The epithelial lining cells are positive for TTF1 (A), CK (B), and are negative for CD31 (C) and CD34 (D) (H&E, 400x).
The patient was well with no recurrence or metastasis at the
1-year follow up evaluation.
Alveolar adenoma (AA) of the lung is a very rare benign
neoplasm. It was reported for the first time by Yousem and
Hochholzer in 1986 2
. In most cases, it occurs in middleaged
and older women, with an age range from 39 to 74
years, and with a mean of 54 years 4
The histogenesis of this tumour remains unknown. The
majority of authors admit that type II pneumocytes are
the origin of the epithelial component 4,5. Some authors,
however, have proposed that the cell of origin in AA is
probably a primitive mesenchymal cell differentiated
toward a type II pneumocyte.
Typically, AA has no clinical manifestations 3,6. Rarely,
the patient can present for chest pain, shortness of breath,
and persistent cough 3. Commonly, AA is discovered by
coincidence on chest X-ray imaging. It presents as a solitary
well-demarcated homogenous mass. The left lower lobe is the
preferential site; however, it can arise in any other lung lobe.
Macroscopic examination shows a subpleural or parenchymal
spongy mass that is well demarcated from the underlying
lung parenchyma 2. It can occur in any lobe, and is
located underneath intact pleura.
Histologically, these tumours have a multicystic appearance.
The cysts are lined with a single layer of flattened or
cuboidal epithelial cells. The cystic lumina are usually filled
with histiocytes, erythrocytes, and periodic acid-Schiffpositive
granular material 2,6. The interstitial component
usually comprises collagen fibrils, spindle cells, or modified
smooth muscle cells. Lymphocytes, mast cells and eosinophils
can be seen in the interstitial areas 2,6,7.
In all reported cases, epithelial lining cells were positive
for TTF-1, CK, surfactant apoprotein A, and Napsin A
which confirms that the lining epithelial cells are type II
pneumocytes, and they are negative for protein S100, and
The diagnosis of AA is extremely difficult when only small
tissue samples are available or on frozen sections. In these
cases, AA could erroneously be diagnosed as malignant
tumour or be considered as normal lung parenchyma 7.
Papillary adenoma, sclerosing hemangioma, atypical adenomatous
hyperplasia, lepidic adenocarcinoma, lymphangioma,
and hamartoma are in the differential diagnosis
of AA 3,7.
Papillary adenoma is also asymptomatic and appears as an
isolated peripheral nodule on chest-X ray. The difference with AA is that papillary adenoma shows an abundant
papillary structure lined with epithelial cells resembling
type II pneumocytes, Clara cells, or ciliated cells. Sclerosing
hemangiomas have the same clinical presentation as AA,
but are histologically distinctive by the association of
four architectural components; papillary, solid, vascular
and sclerotic. The TTF-1 expression observed in AA
is very important to differentiate AA from sclerosing
hemangiomas. Lymphangioma and AA have comparable
histologic features. Only an immunohistochemical study
can differentiate them. Cells lining the cystic spaces in
lymphangioma are positive for factor VIII and CD31, and
negative for CK (7).
The presence of a lepidic pattern, cellular atypia, mitosis,
and a high Ki-67 proliferation index could aid to distinguish
AA from lepidic adenocarcinoma 6. The indolent clinical
progression, the absence of recurrence and metastasis
after complete resection are important to distinguish
AA from adenocarcinoma of the lung. Confirming the
diagnosis on small biopsy sections can be difficult. This
was the case for our patient. The final diagnosis of AA
was made after complete resection. Immunohistochemical
study is not specific. AA cells are positive for TTF-1, and
almost all of them are CK positive; they show a low Ki-67
proliferation index. In accordance with these findings, our
case demonstrated positivity for TTF-1, and CK and the
Ki-67 proliferation index was low.
AA can be mistaken for hamartoma. However, this lesion
is typically composed of a mixture of cartilage, fat, smooth
muscle and bronchiolar tissue 7.
AA is a benign tumour, and complete excision is considered
curative without the need for additional treatment. To the
best of our knowledge, recurrence or metastases have not
been reported 6.
In conclusion, AA presents as an incidental solitary
pulmonary mass. It is entirely benign. AA is a difficult
lesion to diagnose especially on small biopsy specimens.
It is considered as a differential diagnosis of a solitary
pulmonary nodule. We report this case because of its rarity
and good prognosis, and to avoid a misdiagnosis, especially
CONFLICT of INTEREST
The author(s) declared no potential conflicts of interest
with respect to the research, authorship, and/or publication
of this article.
The author(s) received no financial support for the research,
authorship, and/or publication of this article.
The author(s) would like to thank the team of the pathology
department of the Habib Bourguiba University Hospital of
Concept: SG, SM, Design: SG, Data collection or processing:
SG, AH, Analysis or Interpretation: SG, SM, CC, Literature
search: SG, RK, Writing: SG, SM, RK, Approval: TSB.
1) Travis WD, Brambilla E, Burke AP, Marx A, Nicholson AG.
World Health Organization Classification of Tumours of the
Lung, Pleura, Thymus and Heart. 4th ed. International Agency
for Research on Cancer (IARC): Lyon, France, 2015.
2) Yousem SA, Hochholzer L. Alveolar adenoma. Hum Pathol.
3) Kavas M, Öztürk A, Derdiyok O, Atinkaya C, Ürek Ş, Yılmaz A,
Ersev A, Yalcinkaya I. Rare lung tumors: Alveolar adenoma-four
case reports. Turk Thorac J. 2019;20(3):203-5.
4) Wu X, Yuan B, Huang L, Yin X, Liu J. Alveolar adenoma with
poor imaging: A case report. J Int Med Res. 2020;48(3):1-5.
5) Sak SD, Koseoglu RD, Demirag F, Akbulut H, Gungor A.
Alveolar adenoma of the lung. Immunohistochemical and flow
cytometric characteristics of two new cases and a review of the
literature. Apmis. 2007;115:1443-9.
6) Panagiotou I, Kostikas K, Sampaziotis D, Kotoulas C. Alveolar
adenoma: An extremely rare innocent coin lesion. Interact
Cardiovasc Thorac Surg. 2012;14(3):335-7.
7) Burke LM, Rush WI, Khoor A, Mackay B, Oliveira P, Whitsett
JA, Singh G, Turnicky R, Fleming MV, Koss MN, Travis WD.
Alveolar adenoma: A histochemical, immunohistochemical, and
ultrastructural analysis of 17 cases. Hum Pathol. 1999;30:158-67.
8) Halldorsson A, Dissanaike S, Kaye KS. Alveolar adenoma of
the lung: A clinicopathological description of a case of this very
unusual tumour. J Clin Pathol. 2005;58:1211-4.