Bronchial Carcinoid Tumors with Massive Osseous Metaplasia: A Case Report and Review of the Literature
Mine ÖZŞEN1, Ulviye YALÇINKAYA2, Elif Ülker AKYILDIZ2, Ahmet Sami BAYRAM3, Gökhan GÖKALP4
1Department of Pathology, Erzurum Regional Training and Research Hospital, ERZURUM, TURKEY
2Department of Surgical Pathology, Uludag University, Faculty of Medicine, BURSA, TURKEY
3Department of Thorax Surgery, Uludag University, Faculty of Medicine, BURSA, TURKEY
4Department of Radiology, Uludag University, Faculty of Medicine, BURSA, TURKEY
Keywords: Bronchial carcinoid tumor, Carcinoid variants, Osseous metaplasia
Bronchial carcinoid tumors are primary lung neoplasms thought to originate from neuroendocrine cells, i.e. Kulchitsky cells, in the bronchial
mucosa, although the type of cellular origin has not been clearly understood. A 61-year-old male patient underwent surgery and microscopic
examination of the specimen revealed an anastomosing trabecular bony structure among the nests of tumor cells with round nucleus, granular
chromatin, and large eosinophilic cytoplasm. Our case has been deemed worthy of being presented as bronchial carcinoid tumor with exaggerated
Bronchial carcinoid tumors are primary lung neoplasms
thought to originate from neuroendocrine cells, i.e.
Kulchitsky cells, in the bronchial mucosa, although the
type of cell from which they originate has not been clearly
understood. They account for more than 25% of all
carcinoid tumors throughout the body, and less than 1% of
all such lesions in the lung (1,2).
According to the World Health Organization (WHO)
classification in 2015, bronchial carcinoid tumors are
classified into typical and atypical tumors based on their
histopathological characteristics. Another classification
according to the location is as central and peripheral
tumors. Furthermore, there are reports that classify such
tumors as well-differentiated neuroendocrine carcinoma
and moderately-differentiated neuroendocrine carcinoma
according to their histopathological characteristics and
behavioral potential under the heading of neuroendocrine
lung tumors (1,3).
Bronchial carcinoid tumors may present as various
morphologic variants. These variants include tumors
with metaplastic cartilage and bone growth, tumors
containing mucinous stroma, tumors with wide vascular
structures, tumors presenting cystic changes, tumors
presenting glandular pattern, and tumors containing amyloid-like / sclerotic stroma. Although a carcinoid
tumor with metaplastic bone growth is identified as a
variant, exaggerated osseous metaplasia is a rare finding in
carcinoid tumors (4,5).
A 61-year-old male patient presented to an external
medical center with the complaint of persistent cough in
February 2017 and was referred to our hospitals clinic of
pulmonary diseases for further examination and treatment
with the evidence of a pulmonary mass detected during
the thoracic computed tomography (CT) examination
for etiology. The patient had no active complaints during
the admission. The patient was an active smoker for 35
years. There was no specific finding in the patients past
and family history. The patient initially underwent a chest
roentgenogram, followed by a thoracic CT examination.
Thoracic CT examination revealed a mass lesion with
the dimensions of 4x3 cm containing a significant calcific
component in the right hilar region (Figure 1
bronchoscopy (FOB) was planned for histopathological
verification. FOB revealed a complete obstruction of the
right middle lobe due to mucosal irregularity, and a punch
biopsy was performed.
Click Here to Zoom
|Figure 1: Contrast-enhanced thoracic CT scan; mediastinal
window. showing a mass of 37x30 mm in diameter, which results
in a complete obstruction in the right middle lobe bronchus,
leading to an obstructive atelectasis of the middle lobe.
A right lower lobectomy was planned since the biopsy
specimen was identified as a neuroendocrine tumor.
Macroscopical examination of the specimen from the
right lower lobectomy revealed a solid, well-circumscribed
tumoral lesion in the bronchial lumen and parenchyma,
measuring 4x3x3 cm in size, with gray to white crosssectional
areas, and containing locally hard-to-cut regions
Click Here to Zoom
|Figure 2: A) Macroscopical appearance of a solid, well-circumscribed tumoral lesion in the bronchial lumen and parenchyma, with gray
to white cross-sectional areas. B) Nests of tumor cells revealing round nucleus, granular chromatin and large eosinophilic cytoplasm
(H&E; x400). C-D) Nests of tumor cells among anastomosing bone trabeculae (H&E; x100).
Histopathological examination of the lesion following
decalcification and formalin fixation revealed an
anastomosing trabecular bony structure among the nests
of tumor cells with round nucleus, granular chromatin,
and large eosinophilic cytoplasm (Figure 2B-D). No
significant cytological atypia, necrosis or elevated mitotic
activity (<2/10 HPF) were observed in tumor cells with
normal nucleus-cytoplasm ratio. The cells showed strong
positivity with immunohistochemical staining for NSE,
CD56, synaptophysin and chromogranin (Figure 3A-D).
Click Here to Zoom
|Figure 3: Strong positivity to immunohistochemical staining with A) Chromogranin -A (IHC; x100). B) Synaptophysin (IHC; x100).
C) NSE (IHC; x200). D) CD56 (IHC; x100).
There were no findings suggestive of metastasis in any of
the separate lymph nodes, one from station no:11 and three
from the peribronchial region dissected during lobectomy.
Based on histopathological and immunohistochemical
examinations, the case was diagnosed as carcinoid tumor
with exaggerated osseous metaplasia. The patient has been
under clinical follow-up for 17 months and is currently in
complete remission following surgery.
Carcinoid tumors are considered as prototypes of
neuroendocrine tumors, and were first identified by
Langhans in 1867. Gosset and Masson reported in 1914
that these tumors, studied and characterized by various
researchers over time, have endocrine properties (6).
The incidence of bronchial carcinoid tumors ranges from
0.1 to 1.5 / 100,000. Such cases are detected at a younger
age when compared to the primary lung malignancies
(typically under 60 years), and may be seen in a wide range
of ages. Bronchial carcinoid tumors are known to be more
common in females than in males; however, some recent
publications have reported that they have an equal rate of
occurrence in females and males, and some even state they
are 3.6 times more common in males (1,2,7).
Risk factors for developing bronchial carcinoid tumors
include a family history of carcinoid tumors and various
genetic mutations. Although it is known that smoking does
not play a role in the pathogenesis, a history of smoking
is usually present in patients diagnosed with atypical
carcinoid tumor (8,9). In our case, the patient had a history
of smoking for 35 years and there were no carcinoid tumors
in his family history.
Patients with carcinoid tumors usually present with
the complaints of dyspnea and hemoptysis since they
are endobronchial growing masses. One third of the
patients are incidentally detected without presenting any
symptoms depending on the involvement of small airways.
Paraneoplastic syndromes such as Cushing syndrome
and acromegaly can also occur in the cases (10). Our
patient presented with the complaint of a long-lasting and
On radiological examinations, such tumors are seen as
hilar or perihilar masses; however, they may be detected
rarely as peripheral masses as well. While FOB is the
preferred imaging modality for centralized tumors, CT
is the preferred imaging modality for peripheral tumors.
Bronchial carcinoid tumors have a distinctive FOB
appearance as a result of their macroscopical features
including polypoid form, smooth surface, red to bronze
color, and endobronchial growth (11). The diagnosis was
made by a biopsy taken during bronchoscopy performed
following the detection of a hilar mass on CT.
The WHO classifies carcinoid tumors into two categories
according to their histopathological characteristics as
typical and atypical carcinoid tumors. The main criteria
used in such distinction are mitotic activity and necrosis.
In typical carcinoid tumors, which account for 70-90%
of all carcinoid tumors and tend to settle in the center,
the number of mitoses is less than 2 in 10 HPFs, with
no necrosis. The number of mitosis in atypical carcinoid
tumors is between 3 and 9 in 10 HPFs, and focal necrosis
can be detected in such tumors (1,12). No significant
cytological atypia, necrosis or elevated mitotic activity
(<2/10 HPF) was observed in our case.
In bronchial carcinoid tumors, calcification is present
in up to 30% of cases, whereas this number is 10% for
ossification. While calcification requires precipitation
of calcium salts in sites where prolonged tissue damage
occurs due to a number of factors, ossification is a complex
process involving osteoblasts and various inducing
agents. In carcinoid tumor cells, it is thought that both
osteocalcin, defined as an osteogenic differentiation
marker, and secretion of bone morphogenetic protein
(BMP) that induces differentiation of pluripotent cells into
osteoblastic cells have a major role in the ossification in
these tumors. Although there are publications reporting
that intratumoral ossification in different tumors may
be an indicator of metastatic potential, it is currently not
possible to establish a relationship between intratumoral
ossification and metastatic potential due to the insufficient number of cases of carcinoid tumors (13-17). In our case,
there was no evidence suggesting metastasis at the time of
diagnosis and after 17 months of follow-up.
When the literature is reviewed, it is noteworthy that cases
of carcinoid tumors with exaggerated osseous metaplasia
are very rare. The first case was published in 1962, and 23
cases have been reported as case reports so far with no large
series (13-15,18-24). In their first relevant series comprising
22 cases published by Cooney et al. in 1979, ossification was
found in seven cases, five of which were atypical carcinoid
in nature (25). In the series of 63 cases published by Ha et
al. in 2013, ossification was found in six cases, all of which
were typical carcinoid in nature (26).
We conclude that even the typical carcinoid tumors may
present with exaggerated osseous metaplasia, although
extremely rare. Complete resection of such tumors will lead
to cure without any recurrences or metastasis.
CONFLICT of INTEREST
The authors declare no conflict of interest.
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