Liu et al.

Diagnostic Pathology (2022) 17:81 Diagnostic Pathology

https://doi.org/10.1186/s13000-022-01259-8

CASE REPORT Open Access

Pulmonary papillary adenoma with malignant

potential: a case report and literature review
Ping Liu1, Junjian Feng2*, Min Yang3, Jingqiu Chen1, Luyao Fu1 and Junxu Lu1

Abstract
Background Pulmonary papillary adenoma is a rare benign tumor in the periphery of the lung. We report a 66-year-
old female patient with a tumor in the lower lobe of the right lung and present the clinicopathological features and
review the literature.
Case presentation A tumor in the lower lobe of the right lung was found incidentally on chest X-ray during the
physical examination of the patient, and the patient occasionally had a dry cough that was not treated. The tumor
was clearly demarcated and lobulated on CT scan. After 2 years of follow-up, the boundary of the tumor was still clear,
with more lobulations and the enhanced scan showed uniform enhancement. Grossly, the tumor had a granular cut
surface and was easy to fall off, which was helpful for the diagnosis of papillary adenoma during intraoperative frozen
examination. Under the microscope, most areas of the tumor had the typical morphological structure of papillary
adenoma. However, the tumor locally protruded into the surrounding lung tissue, accompanied by crowded cells
and high cell proliferation index. It was suggested that this case of papillary adenoma had malignant potential and
needed active intervention and treatment.
Conclusion Pulmonary papillary adenoma is a rare epithelial tumor with malignant potential. Surgical treatment
should be performed as soon as possible after diagnosis to prevent malignant transformation.
Keywords Pulmonary papillary adenoma, Peripheral tumor, Alveolar adenoma, Lung tumor, Malignant potential

Background potential and reviewed the literature to deepen our

Pulmonary papillary adenoma is a rare benign epithelial understanding of the tumor.
tumor of the lung, which often occurs in the periphery of
the lung. Spencer et al. [1] first reported it in 1980, and 41 Case Presentation
cases have been reported worldwide so far. We reported Clinical history
another case of a papillary adenoma with malignant A 66-year-old female patient underwent a chest X-ray
during the physical examination and incidentally found
a mass in the lower lobe of the right lung 2 years ago.
*Correspondence:
Junjian Feng The patient was previously healthy and had no history of
499420064@qq.com smoking, chest pain, dyspnea and other symptoms, but
1
Department of Pathology, Luzhou People’s Hospital, Jiangyang District, occasionally dry cough. The chest CT scan (November
646000 Luzhou, Sichuan Province, People’s Republic of China
2
Department of Intensive Care Unit, Luzhou People’s Hospital, Section 17, 2018) showed an irregular soft tissue mass in the pos-
2 of Jiugu Avenue, Jiangyang District, 646000 Luzhou City, Sichuan terior basal segment of the lower lobe of the right lung,
Province, People’s Republic of China
3
with a size of about 3.7 cm × 3.4 cm × 2.6 cm, with vis-
Department of Medical Imaging, Luzhou People’s Hospital, Jiangyang
District, 646000 Luzhou, Sichuan Province, People’s Republic of China ible lobulation and clear boundary (Fig. 1 A). The patient

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Liu et al. Diagnostic Pathology (2022) 17:81 Page 2 of 6

Fig. 1 The chest CT scan manifestation of the tumor. A, In 2018, the tumor was well circumscribed, lobulated, and the maximum diameter was 3.7 cm.
B, In 2021, the maximum diameter of the mass was 5.5 cm, with more obvious lobulation. C, Blood vessel was visible in the arterial phase of the tumor

Gross features and intraoperative frozen examination

The tumor was located in the anterior segment of the
upper lobe of the right lung. The surgeon removed the
tumor under thoracoscopy and performed an intraop-
erative frozen examination. Gross examination revealed
a 5.0 cm×4.5 cm×4.0 cm mass in the stump of the par-
tially resected lung without an envelope and has a clear
boundary with the surrounding lung tissue. The cut
surface of the tumor was gray white, solid and granular
(Fig. 2). Moreover, the granular tissue was easy to fall off
when the tumor was incised. Under microscope, the alve-
olar epithelial cell-like tumor cells formed a wide range
of papillary structures with a fibrous vascular core. The
surface of the papilla was covered with a single layer of
cubic to columnar epithelium, cilia were visible, and the
tumor cells were slightly atypical. After discussion by all
pathologists, the final intraoperative pathological diagno-
sis was pulmonary papillary adenoma. Due to the large
tumor, wedge resection was easy to damage the lower
pulmonary artery, vein and bronchial trunk, so the right
lower lobe resection was performed. In order to avoid
the limitation of frozen sampling leading to the upgrad-
ing of pathological diagnosis after freezing, two groups of
regional lymph nodes were cleaned up.

Fig. 2 Grossly, the cut surface of the tumor was gray white, solid and gran- Materials and methods
ular, without an envelope, and has a clear boundary with the surrounding The surgical specimens were fixed in 10% buffered for-
lung tissue malin, embedded in paraffin and serially sectioned into
4-µm-thick slices. Routine staining with hematoxylin and
did not receive treatment. On May 10, 2021, re-exami- eosin (HE) was performed. Representative tissue blocks
nation of chest CT revealed that the volume of the right were also selected for immunohistochemical stain-
lower lobe mass was larger than that in 2018, and the size ing, all antibodies were purchased from Fuzhou Maixin
was about 5.5 cm×5.2 cm×4.2 cm. The mass was well- Company. Primary antibodies included anti-CK20, CK7,
bounded and lobulated without pleural traction (Fig. 1B). TTF-1, NapsinA, Tg, P63, P40, WT-1, Ki67 and P53
The enhanced scan showed uniform and continuous antibodies.
enhancement of the lesion, and the CT value of each
phase was between 75HU and 85HU, and blood vessel Results
was visible in the arterial phase of the tumor (Fig. 1 C). Histologic features
Bilateral hilar and mediastinal structures were clear with- Histologically, the tumor was composed of branched
out enlarged lymph nodes. Peripheral lung cancer was papillae with fibrovascular core, and covering a single
considered in imaging. layer of cubic to columnar epithelium. The fibrovascular
cores were infiltrated with lymphocytes, and few cores
Liu et al. Diagnostic Pathology (2022) 17:81 Page 3 of 6

Fig. 3 Morphological features of the tumor. A, The tumor was composed of branched papillae with fibrovascular cores, and partial papillary cores hyalin-
ized (100×). B, The fibrovascular core was infiltrated with lymphocytes and histiocytes, cilia can be seen (200×). C, The tumor protruded into the surround-
ing lung tissue in a mushroom-shaped without pro-fibrointerstitial reaction around (40×). D, The tumor cells were crowded and arranged pseudostratified
with obvious nucleoli (400×)

hyaline degeneration. And histiocytes were present inside Discussion

and outside of the papillary structures (Fig. 3 A 3B). Cilia Pulmonary papillary adenoma is a very rare benign epi-
can be seen on the luminal s​urface of these epithelial thelial tumor of the lung. So far, 32 cases were reported
cells. The cytoplasm of tumor cells with uniform size was in English, 9 cases were reported in Chinese, and 1 case
eosinophilic or clear, round or oval nucleus. Small nucle- was added in this study. There is no conclusive conclu-
oli can be seen in the nucleus, and eosinophilic inclusion sion about its pathogenesis. Many scholars have found
bodies can be seen in a few nuclei. No necrosis or mito- that both morphology and osmophilic lamellar bodies or
sis was observed. However, the tumor locally protruded electron-dense particles contained in tumor cells were
into the surrounding lung tissue in a mushroom-shaped similar to Clara cells and type II alveolar cells [1–4], so
without pro-fibrointerstitial reaction around (Fig. 3 C). In they considered that it originated from pluripotent stem
addition, the tumor cells in some areas were crowded and cells of bronchioloalveolar epithelium with the potential
arranged pseudostratified with obvious nucleoli (Fig. 3D). to differentiate into Clara cells and type II alveolar cells,
No tumor cell metastasis was observed in regional lymph and may undergo malignant transformation [5–8].
nodes. Patients were usually asymptomatic and most cases
were discovered accidentally during physical examina-
Immunohistochemical staining tions. Majority of the patients were male and ranged
Immunohistochemical staining showed that the tumor in age from 2 months to 78 years old. Tumors mostly
cells were diffusely positive for NapsinA, TTF-1, and occurred in the periphery of the lung and also in the hilar
CK7 (Fig. 4 A 4B 4 C), and negative for Tg, WT-1, P63, region [9], usually with single nodule and occasionally
P40, and CK20, and few cells showed a weak P53 stain- with multiple lesions [10]. The most common location
ing. The Ki-67 proliferative index was about 6%, which was the lower lobe of the left lung, followed by the upper
was higher than 2% ~ 3% reported in the literature, and and lower lobes of the right lung. Only a few patients
even close to 20% in hot spots (Fig. 4D). According to have a history of smoking, indicating that the occurrence
the morphological and immunohistochemical, we con- of tumors was not related with smoking [11].
sidered this to be a case of pulmonary papillary adenoma Under imaging examination, pulmonary papillary ade-
with malignant potential. nomas were mostly solitary round or spherical nodules
Liu et al. Diagnostic Pathology (2022) 17:81 Page 4 of 6

Fig. 4 Immunohistochemical staining of the tumor. A, B, C, The tumor cells were diffusely positive for NapsinA, TTF-1, and CK7 (40×). D, Ki-67 proliferative
index was about 6%, and even close to 20% in hot spots (100×)

with smooth margins in the periphery of the lung. In few cells were clear and there was no mucus in the cells.
some cases, the edges were slightly rough due to malig- The nucleus was usually arranged perpendicular to the
nant transformation of tumors [7]. The lesions showed basal surface of the cell with small nucleoli, and eosino-
lobulation without burr sign, pleural traction or depres- philic inclusions in a few nuclei [12]. The tumor cells
sion, and the enhancement scan showed continuous were mild without mitosis and necrosis. When the tumor
enhancement [12]. Therefore, it was difficult to differen- underwent malignant transformation, the cell atypia was
tiate from sclerosing lung cell tumor, alveolar adenoma, significantly increased, and the polarity disorder, hyper-
and early lung adenocarcinoma on imaging, and the diag- chromatic nucleus, necrosis and nuclear division were
nosis depended on pathological examination. In our case, easy to see [8, 16].
a tumor was discovered in the lower lobe of the right Because pulmonary papillary adenomas were extremely
lung in 2018, and the maximum diameter of the tumor rare, pathologists did not have sufficient knowledge of
increased by about 2 cm after 2 years of follow-up, which the histological morphology of the tumor. In particular, it
still had a clear boundary, but there were more lobulated was easy to be confused with well-differentiated papillary
and passing blood vessels. In enhanced CT scan, the lung adenocarcinoma, sclerosing lung cell tumor domi-
lesions showed uniform continuous enhancement and nated by papillary structure and glandular papilloma dur-
lobulation, which led the radiologist to consider periph- ing intraoperative frozen examination. In the literature,
eral lung cancer. 2 patients underwent intraoperative frozen examination
Pathologic examination showed that the diameter of [10, 17], and 1 case was accurately diagnosed as pulmo-
tumors ranged from 0.2 to 9.5 cm, most of which had no nary papillary adenoma based on its special gross appear-
capsule and were clearly demarcated from surrounding ance [17]. The diagnosis rate was low, so it is particularly
lung tissues. Under the microscope, the tumor was com- important to strengthen pathologists’ understanding of
posed of a large number of branched papillary structures this tumor from the aspect of morphology.
with a fibrous vascular core in the center of the papilla. Immunohistochemical staining showed that tumor
Lymphocytes, plasma cells and histiocytes cell infiltra- cells were diffusely positive for TTF-1, CK7, NapsinA and
tion and hyaline degeneration can be seen in the cores, other alveolar epithelial markers, and negative for CK5/6,
as in our case [13]. The papilla was covered with cubic P63 and neuroendocrine markers. Tumor cell prolifera-
or columnar epithelium, some of which have cilia [14, tion index was usually low, about 2–3% [16], and could
15]. The cytoplasm of most tumors was eosinophilic, a be as high as 25–30% when malignant transformation
Liu et al. Diagnostic Pathology (2022) 17:81 Page 5 of 6

Acknowledgements
occurred [7, 16]. However, no gene mutation related to The authors would like to thank our patient for allowing for his case to be
adenocarcinoma such as EGFR, K-ras or P53 gene was presented.
found by molecular detection regardless of whether the
Authors’ contributions
tumor had malignant transformation [7, 9, 18]. FJJ conceived and designed the study. YM participated in the imaging
Most tumors showed a benign process of slow growth. evaluation of patients. LJX participated in the observation and sampling of
The treatments were mostly segmental resection or pathological specimens. LP participated in the histopathological evaluation,
performed the literature review, acquired photomicrographs and drafted
wedge resection, and a few were lobectomy [16, 19]. The manuscripts. CJQ carried out the immunohistochemical staining, and FLY
patients had a good prognosis and were followed up 6 evaluated it. LP gave the final histopathological diagnosis and revised the
months to 10 years without recurrence and metastasis [2, manuscript. All the authors read and approved the final manuscript.

3, 10]. A few literatures reported that tumors invaded the Funding

surrounding lung tissue, visceral pleura and venules [1, Not applicable.
5–8, 11]. One of the patients developed acinar adenocar-
Data Availability
cinoma and micropapillary adenocarcinoma components All data generated or analysed during this study was included in this
in the same tumor after 2 years of follow-up [7], which published article.
suggested that pulmonary papillary adenoma had malig-
nant potential and should be detected and treated early Declarations
after diagnosis.
Ethics approval and consent to participate
Written informed consent was obtained from the patient. Ethical approval was
Conclusion obtained from the Ethics Committee of Luzhou People’s Hospital, Jiangyang
In summary, pulmonary papillary adenoma is an District, Luzhou 646000, Sichuan Province, People’s Republic of China, in
accordance with the ethical guidelines of the 1975 Declaration of Helsinki.
extremely rare benign epithelial tumor occurring in the Written informed consent was obtained from the patient for publication of
periphery of the lung. The typical structure is a single this case report and any accompanying images. A copy of the written consent
layer of cubic or columnar epithelium on the surface of is available for review by the Editor in-Chief of this journal.

the papilla with a fibrous vascular core. It is easily to be Competing interests

confused with sclerosing lung cell tumor and well-differ- The authors declare that they have no competing interests.
entiated papillary adenocarcinoma by imaging and mor-
Consent for publication
phology, especially during intraoperative frozen section Written informed consent for publication was obtained from all participants.
examination and percutaneous biopsy. Therefore, it is
necessary to combine the patient’s clinical data, imaging Received: 15 November 2021 / Accepted: 4 October 2022
examination, pathological tissue morphology and immu-
nophenotype comprehensive judgment before diagno-
sis to avoid misdiagnosis and mistreatment. At present,
only a few reports support that the tumor has malig- References
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