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1. Primary pulmonary fibrosarcoma with Bone metastasis: A Rare Case Report
Muhammad Redha1 Syamsul Bihar2 Noni Novisari Soeroso3 Elvita Rahmi Daulay4 Lely
hartati5
1 Department of Pulmonology and Respiratory Medicine, Faculty of
Medicine Universitas Sumatera Utara, Adam Malik General
Hospital, Indonesia
2 Intervention Division, Department of Pulmonology and Respiratory
Medicine, Faculty of Medicine Universitas Sumatera Utara, Adam
Malik General Hospital, Indonesia
3 Thoracic Oncology Division, Department of Pulmonology and
Respiratory Medicine, Universitas Sumatera Utara Hospital --
Faculty of Medicine Universitas Sumatera Utara, Indonesia
4 Department of Radiology Medicine, Adam Malik General Hospital --
Faculty of Medicine Universitas Sumatera Utara, Indonesia
5 Department of Anatomical Pathology Medicine, Adam Malik General
Hospital, Indonesia
*Correspondence : Syamsul Bihar. Department of Pulmonology and Respiratory
Medicine, Faculty of Medicine Universitas Sumatera Utara, Universitas Sumatera
Utara Hospital, Jl. Dr. Mansyur No. 66 Medan 20154, Sumatera Utara, Medan,
Indonesia.
E-mail : syamsul_paru@yahoo.com
ABSTRACT
Fibrosarcoma is a rare, highly malignant tumor of mesenchymal cell origin and
arises from pulmonary parenchyma, the bronchi, or the pulmonary artery and its
branches. The positive staining of vimentin demonstrates the mesenchymal origin
of fibrosarcoma. Bone is the third most frequent site of metastases primary lung
cancer. Radical resection is established as the only treatment that can achieve cure

2. or prolonged survival if the tumor seems resectable. Chemotherapy in patients
with advanced-stage fibrosarcomas is based on anthracyclines as the first-line
treatment, which is doxorubicin is the most widely applied drug. The following
report describes cases of fibrosarcoma that were treated with a chemotherapy
regimen.
Keywords: fibrosarcoma, lung cancer, vimentin, chemotherapy
INTRODUCTION
Fibrosarcoma is a rare, highly malignant tumor of mesenchymal cell
origin. It derives from pathologically transformed spindle-shaped fibroblasts with
an excessively high division rate. According to the WHO classification of soft
tissue sarcomas, fibrosarcoma is part of the fibroblastic/myofibroblastic sarcomas.
Two types of fibrosarcoma can be distinguished: the infantile/congenital-type
fibrosarcoma and the adult-type fibrosarcoma. In contrast to the infantile type,
which the WHO has defined as an intermediate malignant rarely metastasizing
tumor, fibrosarcoma occurring in adults is classified as a highly malignant tumor.1
Primary pulmonary sarcomas are extremely rare and can be found in 0.1 to
0.5% of all pulmonary neoplasm cases. The undifferentiated pleomorphic sarcoma
(UPS) is a rare tumor accounting for less than 0.2% of all lung tumors. Lung
metastases from extrapulmonary primary sarcomas have been more frequently
reported than primary pulmonary sarcomas. Primary undifferentiated pleomorphic
lung sarcoma remains an extremely rare malignancy without standardized
treatment and poor prognosis.2 Fibrosarcomas mainly arise in people between the
ages of 25–79. The peak for adult-type fibrosarcoma is between 30 and 60 years
of age.1
Sarcomas in the lungs can arise from pulmonary parenchyma, the bronchi,
or the pulmonary artery and its branches. They typically occur in middle-aged
individuals with a slight predominance in men. Prior history of radiotherapy or
accidental radiation exposure confers greater susceptibility to the development of
sarcomas.3

3. CASE REPORT
Mrs. C, 18 years old Java student, major complained of shortness of
breath, cough, and chest pain. The patient has experienced shortness of breath for
three months. Cough was found in the last months, coughing up white phlegm,
volume ½ tsp per cough, blood was not found, history of coughing up blood was
found six months ago. Chest pain was found on the left, fell like been stabbing
with Vas score: 4 and did not radiate to back. Fever and night sweats were not
found. Weight loss was found, which is a loss of 15 kg in 6 months. History of
exposure to mosquito coils was found for the last ten years.
The patient was previously treated at Rantau Prapat Hospital and only did
a chest X-ray and a non-contrast chest CT scan, then the patient was referred to
Adam Malik Hospital. The patient was a passive smoker for 15 years—the
patient's house was with an abscessed roof and tiled floor in a densely populated
area. The patient works in a residential area.
On physical examination, the patient's consciousness was compos mentis
who looked moderately ill with blood pressure 130/90 mmHg, heart rate 108 bpm,
respiratory rate 26 rpm, SpO2 96% room air, temperature 36.7oC, and VAS: 4.
Head, Neck, Cor, abdomen, and extremities examination within normal limits. On
thoracic examination, proportion anterior and posterior were regular,
asymmetrical with breathlessness on left hemithorax, tactile fremitus left <right,
weakened fremitus in upper to lower left lung. The examination found dim in the
upper to lower left lung on percussion. Auscultation was weak in the upper to
lower left lung. There was no additional sound of rhonchi (-/-) or wheezing (-/-).
Chest X-ray showed a solitary pulmonary mass and minimal pleural
effusion. On MSCT Scan Thorax with IV Contrast examination, a heterogeneous
density mass appeared, post-contrast in upper and middle right lung adhering to
the chest wall and vascular pushing the trachea to right side, left bronchus
narrowing, fluid collection visible in left subdiaphragm, concluded as a left lung
mass with left pleural effusion (T4NXM1A).

4. Figure 1. Chest X-ray examination showed a solitary pulmonary mass
and minimal pleural effusion
Figure 2. MSCT Scan Thorax with IV Contrast examination showed left lung
mass with left pleural effusion (T4NXM1A).
On thorax SPECT examination, there were pathologically increased
radioactivity arrests (multiple hot spots) on the VII cervical vertebrae, I-V
thoracic vertebrae, and left posterior II-III rib. Then it was concluded that there
was a process of bone metastases.

5. Figure 3. thorax SPECT examination showed that there was a process
of bone metastases.
Examination of tumor markers showed LDH 173 U/l, AFP 0.43 ng/ml,
CEA 1.91 ng/ml, β-HcG <1.2 mIU/ml, Cyfra 21-1 0.98 ng/ml, SCC 0.4 ng/ml. On
bronchoscopy, the examination found a tumor in the upper left lung. On
TTLB/TTNA examination with CT SCAN Guidance, histopathological results
were found fragmented mass consisting of pleomorphic tumor cells proliferation
with enlarged nuclei, round oval and spindle shapes, irregular nuclear membrane,
hyperchromatic, eosinophilic cytoplasm. Atypical mitoses were found. The
stroma consists of fibro collagenous connective tissue accompanied by an
infiltration of inflammatory lymphocyte cells. Necrosis and interstitial bleeding
were also seen in several foci. It concluded as spindle cell sarcoma, while on
cytology examination, it was found that smear preparation consisted of pulmonary
TTLB consisting of spindle-shaped cells oval and spindle-shaped nuclei, coarse
chromatin, hyperchromatic, and eosinophilic cytoplasm. The background of the
smear consisted of red blood cells and minimal lymphocytes, then concluded as
C5 (malignant smear), which is a sarcoma (spindle cell).

6. Figure 4. cytology examination showed spindle-shaped cells, oval and
spindle-shaped nuclei, coarse chromatin, hyperchromatic, and eosinophilic
cytoplasm. A, B : Magnification 100x; C,D : Magnification 400x
On immunohistochemical examination, it was found that vimentin was
positively stained with diffuse staining of tumor cells, AE1/3, CD 30, CD 45 was
negative, and it was concluded that this case was more in line with Sarcoma
(Fibrosarcoma). The patient was then diagnosed with primary pulmonary
fibrosarcoma and treated with chemotherapy.
100x 100x
400x 400x

7. Figure 5. AE1/3, CD 30, CD 45 immunohistochemical examination
was negative - unstained tumor cell. Magnification 40x and 200x
AE1/3, 40x AE1/3, 200x
CD 30, 40x CD 30, 200x
CD 45, 200x

8. Figure 6. Vimentin immunohistochemical examination was positively
stained with diffuse staining of tumor cells. Magnification 40x and 200x
DISCUSSION
Primary pulmonary fibrosarcoma was an extremely rare lung neoplasm
that has accounted for about 12% of all pulmonary tumors in infants and young
children. Fibrosarcoma of the lung could arise from the trachea, bronchus,
pulmonary parenchyma, or pulmonary artery. Fibrosarcoma has been shown as a
heterogenous group of malignant mesenchymal origin tumors classified as non-
rhabdomyosarcoma Soft Tissue Sarcoma (NRSTS).4 Sarcomas are relatively
uncommon tumors accounting for approximately 1% of all adult cancers.5
Primary pulmonary sarcomas are rare tumors, representing about 40 % of "rare"
pulmonary neoplasms and 9 % of all sarcomas.3
Postoperative pathology of the resected specimen showed undifferentiated
pulmonary sarcoma (UPS), pT4N0M1a stage IV A and genetic analyses revealed
the v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. Li
et al. reported a case of concurrent KRAS mutation and phosphatidylinositol 3-
kinase p110 subunit alpha (PIK3CA) mutation. Serrano et al. also reported that
the RAS/mitogen-activated protein kinase (Ras/MAPK) and phosphatidylinositol
3-kinase (PI3K)/mTOR pathways were activated in the majority of patients with
UPS. KRAS is a proto-oncogene located at 12p12.1, and a frequently altered
gene, with mutations occurring in 17–25% of all cancers. Constitutive activation
of growth factor signaling pathways is responsible for maintaining aggressiveness
and tumor phenotype, and among the pathways, the RAS/MAPK and
Vimentin 40x Vimentin200x

9. PI3K/mTOR pathways commonly drive oncogenic stimuli in soft tissue
sarcomas.6
From History Talking should always include detailed symptom-based
questions of pain, paraesthesia, changes in the size and consistency of the soft
tissue mass, and former lesions, surgical interventions, and prior radiation
therapies. Anamnesis should always include a thorough medical and family
history.1 Criterion for suspicion of soft-tissue sarcomas (STS) and the need to
contact a reference center is a soft tissue mass often painful, greater than 5 cm or
progressively increasing in size, located under the deep fascia relapse after an
inadvertent excision.7
Fibrosarcomas are often found in deep soft tissue. The tumor mass is
characterized by a firm consistency, a spherical shape, a sharp demarcation from
the surrounding tissue, and an average 3–8 cm size. Due to its sometimes deep
localization, the rather unspecific and often painless soft-tissue swelling, this
tumour may remain undetected for a long time ("tip-of-the-iceberg"
phenomenon). The final stages of fibrosarcoma may be accompanied by anorexia,
weight loss, and reduced performance.1
Alternatively, computed tomography (CT) or X-ray can help detect bone
involvement. CT of the chest and abdomen/pelvis or an MRT of the whole body
or positron emission tomography (PET)-CT can assist in the detection of distant
metastases. A minimal invasive procedure such as fine-needle aspiration (FNA)
biopsy or the core needle biopsy can be used. If the tumor exceeds the size of 3
cm and if minimal invasive methods have failed, surgical biopsies are indicated.
Soft tissue tumors ranging between 3 and 5 cm in size should be biopsied via
excisional biopsy. If the tumors exceed the size of 5cm, incisional biopsies can be
conducted where only a part of the tumor is resected.1
The skeleton is the third most frequent site of metastases from solid
tumors, and the vast majority of bone metastases affect patients with primary
breast, lung, or prostate cancer. In the Vincenzi study, less than five bone
metastases were detected in 60% (81/135) of patients. Among the analyzed
patients, the spine was involved in 51% (69/135) of cases, being the most

10. common skeletal site; hip/pelvis was involved in 20% (27/135) of patients, long
bones in 15% (20/135), and other sites 14% (19/135). Radiotherapy was used in
almost one-third of the patients mainly to improve pain control or reduce the risk
of a pathological fracture, while surgery was limited to 21% of the cases. Patients
survived for a median of 6 months after diagnosis of bone metastases (range: 1–
14).9
Immunohistochemistry has an essential role in accurately diagnosing and
classifying sarcoma types. It is often positive for keratin, actin, desmin, EMA,
CD99, and CD34, but positive stains usually do not help diagnosis, so UPS is a
diagnosis of exclusion. Microscopic description characteristic for UPS was also
present in the tumor tissue of our patient: storiform pattern, irregular fascicles,
variable cellularity, and pleomorphic and bizarre tumor cells with foamy
cytoplasm and marked atypia; on the background of inflamed collagenous stroma,
multinucleated giant cells were seen, also numerous mitotic figures, including
atypical forms.2
Fibrosarcoma is characterized by its parallelly arranged monomorphic
spindle-shaped fibroblasts. Often, these strands of fibroblasts are angled
perpendicular to each other, which causes the impression of a herringbone pattern.
The nuclei are prominent with a variable number of nucleoli and an increased
irregular, coarse, granular chromatin; with limited cytoplasm. Pleomorphism is
rare. The amount of necrotic and hemorrhagic tissue, interstitial collagen, and
mitotic cells correlates with the stage of tumor malignancy. Histopathology alone
is not sufficient for a clear distinction between fibrosarcoma and other spindle-cell
neoplasms.1
The positive staining of vimentin demonstrates the mesenchymal origin of
fibrosarcoma. Desmin, alpha-smooth muscle actin (α-SMA), and muscle-specific
actin (MSA) are the most common myogenic markers. The S-100 protein is a
neuronal marker that excludes malignant peripheral nerve sheath tumors
(MPNST). Upbeat CD 31, CD34, and factor VIII (von Willebrand factor)
immunostains point to vascular malignancies e.g., spindle-cell angiosarcomas. In
fibrosarcoma, vimentin is often the only positively stained marker. Sometimes

11. muscle-specific antigen (MSA) and/or smooth muscle actin (SMA) can be
detected as signs of myofibroblastic differentiation. In those fibrosarcomas which
arise secondarily from either solitary fibrous tumor (SFT), CD34 can sometimes
be detected.1
Radical resection is established as the only treatment that can achieve cure
or prolonged survival if the tumor seems resectable.2 The decision should be
based on the disease-free period following primary surgery (ideally more
significant than one year) and the possibility of resection with negative margins
rather than the number of lesions (III, B). Complete resection of pulmonary
metastases in these selected patients achieves up to 20% long-term survival.7 The
primary treatment of fibrosarcoma has involved complete surgical resection of the
tumor. The possibility of complete resection of the tumor has increased the
chances of recovery and non-recurrence of disease.4
On the other hand, the role of perioperative chemotherapy is still
controversial. These neoplasms have an aggressive clinical course with a high
potential for recurrence and metastasis. In an advanced stage, a combination of
chemotherapy or radiotherapy may be used as a palliative approach, although the
tumor seems insensitive to both chemotherapy and radiotherapy.2 Complementary
radiotherapy (RT) can be offered in addition to surgery to optimize local control.
Two prospective randomized trials, one using brachytherapy (BRT) and the other
with postoperative external beam RT (EBRT), demonstrated the local control
advantage of adjuvant RT over surgery alone in sarcomas.7 The recommended
postoperative radiation dose is 60–66 in 1.8–2 Gy fractions.5
Chemotherapy in patients with advanced-stage fibrosarcomas is based on
anthracyclines as the first-line treatment. In this context, doxorubicin is the most
widely applied drug. Besides doxorubicin, actinomycin D and ifosfamide can
reach response rates above 15%.1 In lung cancer, significant advances have been
made in treatment with the advent of immune-checkpoint inhibitors such as
nivolumab (anti-programmed cell death 1 [PD-1] antibody), pembrolizumab (anti-
PD-1 antibody), durvalumab (anti-PD-L1 antibody), atezolizumab (anti-PD-L1
antibody), and ipilimumab (anti-cytotoxic T lymphocyte antigen four antibodies).6

12. Preoperative pulmonary rehabilitation (Prehab) has been shown to
significantly improve symptoms of dyspnoea, exercise capacity, and quality of life
in patients with COPD; following lung volume reduction surgery; or lung
transplantation. Loss of lung tissue in such patients may grossly impair
postoperative ventilatory function or diffusion capability, predisposing them to
dyspnoea, cardiopulmonary complications, and death. Hence, some patients with
borderline or poor pulmonary function are considered in-operable and referred for
radiotherapy, systemic anticancer treatment, or palliative care instead. High-risk
patients can be optimized with preoperative and postoperative pulmonary
rehabilitation to reduce their frequency of postoperative pulmonary complications,
hospital stay and improve postoperative outcomes, including mortality.8
Prognostically, unfavorable factors of fibrosarcoma include (i) high
histologic grade, (ii) large amount of tissue necrosis (> 50%), (iii) a high number
of mitotic figures (> 20/10 HPF), (iv) a decrease of collagen fibers in favor of
increased cellularity, (v) intensely localized tumors, (vi) and tumors exceeding the
5 cm. Depending on the tumour grade, the patient's age and the histology of the
tumour margin, the recurrence rate lies between 12 and 79%, averaging in the
40% to 50% range need to be esbablished. In 10–20% of patients whose tumors
had been adequately resected, recurrences occur within five years.1
CONCLUSION
Fibrosarcoma is a rare, highly malignant tumor of mesenchymal cell
origin. Sarcomas in the lungs can arise from pulmonary parenchyma, the bronchi,
or the pulmonary artery and its branches. The tumor mass is characterized by a
firm consistency, a spherical shape, a sharp demarcation from the surrounding
tissue, and an average 3–8 cm size. The positive staining of vimentin
demonstrates the mesenchymal origin of fibrosarcoma. Bone is the third most
frequent site of metastases primary lung cancer. Radiotherapy was used in almost
one-third of the patients mainly to improve pain control or reduce the risk of a
pathological fracture. Radical resection is established as the only treatment that
can achieve cure or prolonged survival if the tumor seems resectable.

13. On the other hand, the role of perioperative chemotherapy is still
controversial, and complementary radiotherapy (RT) can be offered in addition to
surgery to optimize local control. Chemotherapy in patients with advanced-stage
fibrosarcomas is based on anthracyclines as the first-line treatment, which is
doxorubicin is the most widely applied drug. In 10–20% of patients whose tumors
had been adequately resected, recurrences occur within five years
REFERENCES
1. Augsburger D; Nelson PJ; Kalinski T; Udelnow A; Knosel T; Hofstetter
M; et al. Current diagnostics and treatment of fibrosarcoma –perspectives
for future therapeutic targets and strategies. Oncotarget, 2017, Vol. 8, (No.
61), pp: 104638-104653
2. Plestina S; Librenjak N; Marusik A; Vuletic LB; Janevski Z; Jakopovic M.
An extremely rare primary sarcoma of the lung with peritoneal and small
bowel metastases: a case report. World Journal of Surgical Oncology
(2019) 17:147
3. Goncalves MJ; Mendes MM; Joao F; Lopes JM; Honavar M. Primary
pleomorphic sarcoma of lung — 11 year survival. Rev Port Pneumol.
2011;17(1):44-47
4. Hiradfar A; Pourlak T; Badebarin D. Primary Pulmonary Fibrosarcoma
With Bone Metastasis: a Successful Treatment With Post-Operation
Adjuvant Chemotherapy Iran J Cancer Preven. 2015 May; 8(3):e2328.
5. Dangoor A; Seddon B; Gerrand C; Grimer R; Whelan J; Judson I. UK
guidelines for the management of soft tissue sarcomas. Clin Sarcoma Res
(2016) 6:20
6. Higuchi M; Yamada H; Machino K; Oshibe I; Soeta N; Saito T; et al.
Successful Multidisciplinary Treatment for Aggressive Primary
Pulmonary Undifferentiated Pleomorphic Sarcoma. Case Rep Oncol
2020;13:385–391

14. 7. Lopez-Pousa A; Broto JM; Trufero JM; Sevilla I; Valverde C; et al.
SEOM Clinical Guideline of management of soft-tissue sarcoma (2016).
Clin Transl Oncol (2016) 18:1213–1220
8. Goldsmith I; Chesterfield-Thomas G; Toghill H. Pre-treatment
optimization with pulmonary rehabilitation in lung cancer: Making the
inoperable patients operable. EClinicalMedicine 31 (2021) 100663
9. Vincenzi B; Frezza AM; Schiavon G; Santini D; Dileo P; Siletta M; et al.
Bone metastases in soft tissue sarcoma: a survey of natural history,
prognostic value and treatment options. Clinical Sarcoma Research 2013,
3:6