Get Permission Kinkhede, Meshram, Parate, Kumbhalkar, Tathe, and Randale: Histomorphological spectrum of intracranial space occupying lesions: Experience at tertiary care centre


Introduction

An “Intra-cranial space occupying lesion” (ICSOL) is defined as mass lesion in the cranial cavity with a diverse etiology like benign or malignant neoplasm, inflammatory or parasitic lesion, haematoma or arterio-venous malformation.1

ICSOLs can be caused due to cysts, cerebrovascular disorders, infections, tumours.

The most common cause of ICSOL is neoplastic followed by non-neoplastic lesions.

CNS (central nervous system) neoplasms represent a unique, heterogenous population of neoplasms constituting 1.9% of all malignant tumors in India.

Tumours of CNS account for 2% of all cancers in adults and 20% in childhood.2

Moreover, the CNS tumours that predominate in adults differ from those seen in children, in terms of frequency, histological type and location.3

ICSOLs can clinically present as headache, vomiting, seizures, behavioural problems, focal deficits and visual difficulties.4

Radiological assessment helps in diagnosing the presence of an ICSOL, its location and its nature- whether benign or malignant, changes in the lesion like necrosis, intratumoural haemorrhage, surrounding edema and mass effect caused by ICSOL.5

But radiological imaging cannot give exact diagnosis of the ICSOL.

For definitive diagnosis, histopathology remains the gold standard for diagnosis and grading of tumours, based on which treatment protocol of patient is determined.

In developing countries like India due to lack of complete registration of newly diagnosed cases, exact tumour burden goes unnoticed and is underestimated. Hospital based data, therefore, forms the basis for estimating the disease load.6

The present study attempts to provide information about the histopathological spectrum of ICSOL at a tertiary care centre/ hospital in order to give accurate pretherapeutic histomorphological diagnosis helping to facilitate better therapeutic results.

Materials and Methods

This prospective and descriptive type of study of two years duration was carried out from November 2017 to October 2019 in Govt. Medical College and Superspeciality Hospital, Nagpur in the Department of Pathology. A total of 300 samples were received from Department of Neurosurgery.

Inclusion criteria

All biopsy/ resected specimen of ICSOLs.

Presence of ICSOL in patients was confirmed on radiological imaging.

Exclusion criteria

  1. Haematoma and arteriovenous malformations.

  2. Bony lesions of skull.

  3. Spinal cord lesions.

Detailed collection of clinical data was done in all patients regarding age, sex, clinical symptoms and radiological findings. Informed consent was obtained from patients.

The samples were received in 10% formalin in labelled containers which comprised of biopsies or resected specimens.

The samples received were usually in multiple tissue pieces, mostly grey white to grey black in colour which were then subjected to routine histopathological processing. Slides prepared were stained with hematoxylin and eosin stain. Special stains were done wherever necessary.

Histomorphologically, ICSOLs were classified as neoplastic and non neoplastic lesions. The tumours were classified according to the WHO classification of tumours of central nervous system.7

Statistical analysis was performed using Microsoft Excel software.

The study was approved by institutional ethical committee.

Results

A total of 300 resected tumours/ biopsies were studied. Radiological and histomorphological diagnosis was available in all 300 cases.

The most common age group affected was 31-40 years (23.68%) followed by 41-50 years of age group (20.33%). The average age was 36.33 years.

55 cases belonged to the paediatric age group.

Out of 300 cases, 169 (56%) were male and 131 (44%) were female. The male to female ratio was 1.3:1.

In males, 41 cases were seen in the age group 31-40 years followed by 35 cases in 41-50 years of age.

Similarly, in females, highest number of cases (30 cases) were seen in 31-40 years of age group followed by 26 cases in 41-50 years of age and 24 cases in 21-30 years of age. (Figure 1)

Figure 1

Showing age and sex wise distribution of cases

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/1bdd1424-a0c9-45d6-ad6a-3facc7356e03-uimage.png

The most common clinical presentation in patients was headache (78%) followed by vomiting (32%), loss of consciousness (22%), convulsions (17%) and diminution of vision (17%).

220 cases (73%) were located supratentorially and 80 cases (27%) infratentorially.

The distribution of ICSOLs in each compartment is given in Table 1.

Table 1

Distribution of ICSOL in each compartment

S. No

Location

No of cases

%

1

Supratentorial

220

73

Frontal lobe

48

16

Temporal lobe

23

7.7

Parietal lobe

37

12.3

Occipital lobe

4

1.3

Multiple lobes

59

19.7

Suprasellar & sellar region

34

11.3

Corpus callosum

3

1

Lateral ventricles

7

2.3

Pineal region

1

0.3

Thalamus

2

0.7

Parasagittal region

2

0.7

2

Infratentorial

80

27

CP angle

32

10.7

Cerebellum

35

11.7

Fourth ventricle

12

4

Midbrain

1

0.3

Total

300

100

Out of 300 ICSOLs, 261 cases (87%) were neoplastic in nature and 39 cases (13%) were non neoplastic.

Out of 261 neoplastic ICSOLs, 250 cases (96%) were of primary tumours and 11 cases (4%) were of metastatic deposits. Amongst primary tumours, 124 cases (48%) were of glioma followed by 51 cases (20%) of meningioma and 24 cases (9%) of schwannomas. Distribution of neoplastic ICSOLs is given in Table 2.

Table 2

Distribution of neoplastic ICSOLs based on histomorphology

S. No

Histomorphological subtypes

No cases

%

1

Glioma

124

48%

2

Meningioma

51

20%

3

Schwannoma

24

9%

4

Pituitary adenoma

18

7%

5

Craniopharyngioma

12

5%

6

Hemangioblastoma

6

2%

7

Medulloblastoma

4

1.1%

8

Choroid plexus papilloma

3

1%

9

Central neurocytoma

2

0.7

10

Cavernous angioma

2

0.7

11

Germ cell tumour

2

0.7

12

Pineoblastoma

1

0.4

13

Non Hodgkin’s lymphoma

1

0.4

14

Metastatic tumour

11

4

Total

261

100

In gliomas, the most common type was glioblastoma (51 cases, 41.1%) followed by astrocytomas (22 cases, 18%). Out of 51 cases of glioblastomas, 35 cases (68.6%) belonged to age group 31-60 years. (Figure 2)

Figure 2

Distribution of gliomas based on histomorphology (n=124 cases)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/caf97694-ed1e-458d-83fa-933b61e77d0e-uimage.png

Amongst meningiomas, the most common subtype was meningothelial meningioma (25 cases, 49.03%). (Table 3)

Table 3

Distribution of meningioma variants based on histomorphology

S. No

Histopathological diagnosis

No of cases

%

1

Meningothelial

25

49.03

2

Transitional

6

11.76

3

Angiomatous

4

7.84

4

Fibrous (Fibroblastic)

3

5.88

5

Clear cell

2

3.92

6

Psammomatous

2

3.92

7

Chordoid

1

1.96

8

Atypical

8

15.69

Total

51

100

Female preponderance of 29 cases (57%) was noted in meningiomas.

Tumours were graded according to WHO criteria.7

Out of 250 primary tumours, pituitary adenomas, lymphomas, cavernous angiomas and germ cell tumours were not assigned grades.

Grade I tumours were in majority (41%) followed by grade II and IV tumours which were 24% each and grade III tumours (11%). (Figure 3)

Figure 3

Showing grade wise distribution of all cases

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/e175b7ad-6f72-4134-902c-5faae976574b-uimage.png

Out of 39 cases of non neoplastic ICSOL the most common was abscess (16 cases, 41.02%) closely followed by epidermoid cyst (15 cases, 38.46%). Other non neoplastic lCSOLs encountered were tuberculomas (12.82%), hydatid cyst (5.14%) and Rathke’s cleft cyst (2.56%).

Table 4

Comparison of histomorphological subtypes of neoplastic ICSOLs with other similar studies

S. No

Author

Year

Gliomas

Meningiomas

Schwannomas

1

Butt et al

2005

43%

25.8%

12%

2

Kothari et al

2014

40%

22%

6%

3

Lakshmi et al

2015

50.7%

23.6%

5.5%

4

Dogar et al

2015

46%

13%

--

5

Anadure et al

2016

50%

12.5%

14%

6

Adnan et al

2017

35.4%

22.9%

8.6%

7

Kaki RR et al

2017

28%

-

6%

8

Shihora et al

2020

33.3%

25.5%

21.57%

9

Khonglah et al

2020

27.8%

20.97%

18.4%

10

Present study

2019

47.5%

19.5%

9%

Figure 4

Photomicrograph of oligidendroglioma showing cells in sheets with perinuclear haloes (Fried egg appearance) and foci of calcification. (HE, 40x)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/e7901832-0a2a-478b-8687-63c333df6bff-uimage.png

Figure 5

a): MRI of glioblastoma (GBM) showing an irregularly shaped SOL with ring enhancement in temporoparietal lobe; b): Photomicrograph of glioblastoma showing pseudopalisading necrosis surrounded by tumour cells. (HE, 4x)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/2957ba93-0834-43ea-a78c-4b0477fbf2d1-uimage.png

Figure 6

Photomicrograph of schwannoma showing Antoni A areas of compactly arranged tumours and Verocay bodies with loosely arranged Antoni B areas. (HE,10x)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/15c13c41-c575-4ee7-aaed-57b437a26fd7-uimage.png

Figure 7

a): Gross specimen of meningioma which is firm, round, well circumscribed with attached dura; b): Photomicrograph of meningothelial meningioma showing uniform cells with oval nuclei and abundant eosinophilic cytoplasm. (HE, 40x)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/be098fd6-b643-4dad-9cfe-080f67de5143-uimage.png

Figure 8

Photomicrograph of metastatic deposits of adenocarcinoma showing tumour arranged in papillary pattern with necrotic glial tissue. (HE, 10x)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/d0996a76-77a4-44c2-beb6-55a01aad9ee0-uimage.png

Figure 9

Photomicrograph of pituitary adenoma showing tumour arranged in sheets. Cells show round to oval nuclei with fine granular chromatin. (HE, 40x)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/227578ea-fab5-4717-886b-72b3fbaa52d8-uimage.png

Figure 10

Photomicrograph of tuberculoma showing caseous necrosis, Langhans giant cell surrounded by lymphocytes and reactive glial tissue. (HE, 10x)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/3eaa11b5-1379-4d61-b8ce-afcde67652eb-uimage.png

Figure 11

a): Gross specimen of hydatid cyst showing smooth, glistening, whitish appearance. b): Photomicrograph of acellular, lamellated eosinophilic hydatid cyst wall. (HE, 10x)

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/1fd8fbdd-e71b-422a-80e4-9795fafa0db9-uimage.png

Figure 12

Photomicrograph of Rathke’s cleft cyst lined by cuboidal to columnar epithelium

https://typeset-prod-media-server.s3.amazonaws.com/article_uploads/213330a2-c662-4686-9a25-922dbea2ab45/image/654706af-e0fb-4bbe-8d00-2f4da5d9bcfa-uimage.png

Discussion

The present study is an attempt to assess the histomorphological spectrum of ICSOLs at a tertiary care centre/ hospital.

The most common age group affected was 31-40 years (23.68%) followed by 41-50 years of age group (20.33%). Studies by Hema et al, Masoodi et al, Dogar et al, Pachori et al, Khonglah et al and Shihora et al also showed maximum cases in the age group 31-40 years.2, 8, 9, 10, 11, 12

The male to female ratio was 1.3:1. Our finding was similar to studies by Chawla et al, Nibhoria et al, Rathod et al, Butt et al, Adnan et al, Joshi et al.4, 6, 13, 14, 15, 16

The most common clinical presentation was headache (78%). Hema et al, Masoodi et al, Khonglah et al, Rathod et al, Joshi et al, Kaki RR et al and Datta et al also reported similar observation.2, 8, 11, 13, 16, 17, 18

Out of total 300 cases, 220 cases (73%) were located supratentorially and 80 cases (27%) infratentorially. These findings were seen to correspond with studies by Jamjoom et al, Masoodi et al, Pachori et al and Kaki RR et al.1, 8, 10, 17

In supratentorial compartment, majority (19.7%) of cases showed multiple lobe involvement followed by 48 cases (16%) involving frontal lobe. Masoodi et al and Shashidhar et al reported 21.7% and 30% of multiple lobe involvement respectively in their study.8, 19 20.7%, 23%, 10%, 15.5% of ICSOLs were located in frontal lobe in studies by Masoodi et al, Shashidhar et al, Lakshmi et al and Thambi et al respectively.8, 19, 20, 21 These findings correlated well with our study.

In infratentorial compartment, 35 cases (11.7%) showed involvement of cerebellum followed by 32 cases (10.7%) involving cerebellopontine angle (CP) angle. Suprasellar and sellar region, cerebellum and CP angle showed variable distribution across multiple studies.8, 12, 19, 20, 21

Out of 300 cases, 261 cases (87%) were neoplastic in nature and 39 cases (13%) were non neoplastic. Jamjoom et al, Dogar et, Khonglah et al, Butt et al and Adnan et al reported 87%, 89%, 86.13%, 89% and 77.8% of neoplastic ICSOLs and 13%, 11%, 13.86%, 11% and 22.2% of non neoplastic ICSOLs respectively.1, 9, 11, 14, 15

250 cases (96%) were of primary tumour and 11 cases (4%) were of metastatic deposits. These findings were in agreement with studies by Hema et al, Nibhoria et al, Khonglah et al, Shihora et al, Butt et al, Joshi et al, Kaki RR et al, Lakshmi et al and Kanthikar et al.2, 6, 11, 12, 14, 16, 17, 20, 22

Out of 261 neoplastic ICSOLs, majority belonged to gliomas (48%) followed by meningiomas (20%) and schwannomas (9%). (Table 4) Hema et al, Dogar et al, Khonglah et al, Butt et al, Adnan et al, Kaki RR et al, Lakshmi et al and Kothari et al reported 50%, 46%, 27.8%, 43%, 35.4%, 28%, 50.7% and 40% of glial tumours respectively in their studies.2, 9, 11, 14, 15, 17, 20, 23

In case of meningiomas our findings were in agreement with studies by Khonglah et al, Shihora et al, Butt et al, Adnan et al, Joshi et al, Datta et al and Kothari et al. 11, 12, 14, 15, 16, 18, 23 Studies by Pachori et al (42.8%) and Kaki RR et al (32%) reported higher percentage of meningiomas.10, 17

Studies by Hema et al (14%), Butt et al (12%), Adnan et al (8.6%), Kaki RR et al (6%), Datta et al (6.5%), Lakshmi et al (5.5%) and Kothari et al (6%) showed similar distribution of schwannomas as in present study.2, 14, 15, 17, 18, 20, 23 A higher percentage of schwannomas was noted in studies by Khonglah et al (18.04%), Shihora et al (21.57%) and Joshi et al (22.6%).11, 12, 16

Amongst gliomas, in our study the most common type was glioblastoma (41.1%) followed by astrocytomas (18%). Our findings were concordant with studies by Masoodi et al, Pachori et al, Khonglah et al, Adnan et al, Thambi et al and Kakshapati et al.8, 10, 11, 15, 21, 24

68.6% of glioblastomas belonged to age group 31-60 years. Masoodi et al reported that 75% of glioblastomas in age group 31-50 years and Khonglah et al observed a mean age of 42.38 years.8, 11 Adnan et al too reported most cases of glioblastoma above 40 years.15

In present study, the most common histologic subtype amongst meningiomas was meningothelial meningioma represented by 25 cases (49.03%) followed by 8 cases of atypical meningioma (15.69%) and 6 cases of transitional meningioma (11.76%). Other studies showed variable distribution of histomorphological subtypes of meningioma.2, 6, 11, 12, 19, 24, 25, 26, 27

Meningiomas showed female predominance of 29 cases (57%). Our findings were concordant with studies by Nibhoria et al, Khonglah et al, Adnan et al, Kakshapati et al and Priscilla et al.6, 11, 15, 24, 26

In our study, grade I tumours were in majority (41%) followed by grade II and IV tumours which were 24% each and grade III tumours (11%). Similar findings were also observed in studies by Shihora et al, Kakshapati et al, Jat et al, Priscilla et al and Jaiswal et al.12, 24, 25, 26, 28

Out of 300 ICSOLs, the most common non neoplastic ICSOL was abscess (5.3%) closely followed by epidermoid cyst (5%). Jamjoom et al, Hema et al, Shihora et al, and Joshi et al reported 6.6%, 6.5%, 3.07% and 8.3% of abscesses respectively, out of all ICSOLs.1, 2, 12, 16

1.54%, 3.1%, 2.27% of epidermoid cysts out of all ICSOLs were observed in studies by Shihora et al, Joshi et al and Sunila et al respectively.12, 16, 27

In present study, 55 cases (18.33%) belonged to paediatric age group.

Similar findings were reported by Nibhoria et al – 12.3%, Khonglah et al (23.41%), Butt et al - 18% and Jaiswal et al – 16.2%.6, 11, 14, 28

Conclusion

The present study gives a glimpse of histomorphological spectrum of ICSOLs which present with nonspecific and overlapping clinical features.

Radiodiagnostic investigations are helpful adjunct tool to diagnose ICSOL but cannot provide exact diagnosis.

In spite of availability of newer diagnostic techniques such as immunohistochemistry and molecular tests, histopathology remains a gold standard in establishing histomorphological diagnosis and grading of tumours.

In the end, clinical, radiological and histomorphological findings- all three must be taken into account before giving the final diagnosis which can help the clinician in deciding the line of management and improve patient healthcare.

Also developing countries lack a central cancer registry for brain tumours. Hence, such hospital based study attempts to give relative frequency of ICSOLs in a particular region.

Source of Funding

None.

Conflict of Interest

The authors declare no conflict of interest.

References

1 

ZAB Jamjoom Pattern of intra-cranial space occupying lesions: experience at King Khalid University HospitalAnn Saudi Med19899310

2 

NA Hema RS Ravindra AS Karnappa Morphological Patterns of Intracranial Lesions in a Tertiary Care Hospital in North Karnataka: A Clinicopathological and Immunohistochemical StudyJ Clin Diagn Res2016108105

3 

G Aryal Histopathological pattern of central nervous system tumour: A three year retrospective studyJ Pathol Nepal20111225

4 

N Chawla SP Kataria S Malik N Sharma S Kumar Histopathological spectrum of CNS tumours in a tertiary care referral centre-A one year studyInt J Basic Appl Med Sci2014421414

5 

N Jindal SR Verma PK Gupta M Mital Imaging of Intracranial Space Occupying Lesions: A Prospective Study in A Tertiary Care Centre in Northern IndiaIOSR J Dent Med Sci2016155344110.9790/0853-1505093441

6 

S Nibhoria K K Tiwana R Phutela A Bajaj S Chhabra S Bansal Histopathological Spectrum of Central Nervous System Tumors: A Single Centre Study of 100 CasesInt J Sci Stud2015361304

7 

DN Louis H Ohgaki OD Wiestler WK Cavenee WHO Classification of tumours of the central nervous system4th EditionIARCLyon2007

8 

T Masoodi RK Gupta JP Singh A Khajuria Pattern of Central Nervous System Neoplasms: A Study of 106 CasesJK-Practitioner2012174426

9 

T Dogar AA Imran M Hasan R Jaffar R Bajwa ID Qureshi Space occupying lesions of central nervous system: A radiological and Histopathological CorrelationBiomedica2015311520

10 

G Pachori NR Dixit A Sirohi N Kasliwal N Jethani R Sunaria Clinicopathological Study of CNS Tumors in Ajmer RegionInt J Med Res Prof201844261510.21276/ijmrp.2018.4.4.060

11 

Y Khonglah D Shangpliang J Mishra A Mustafa A Kakoti P Phukan Histological spectrum of central nervous system lesions at a tertiary care center in IndiaClin Cancer Investig J2020917581

12 

NV Shihora HU Patel SM Patel PR Ramani BN Nandasana A study of histopathological spectrum of central nervous system lesions at a tertiary health care center of South Gujarat, IndiaInt J Res Med Sci2020814517

13 

V Rathod A Bhole M Chauhan H Ramteke B Wani Study of clinicoradiological and clinico-pathological correlation of intracranial space occupying lesion at rural centerInternet J Neurosurg20097116

14 

ME Butt SA Khan NA Chaudrhy GR Qureshi Intracranial Space occupying lesions - A morphological analysisBiomedica200521315

15 

HA Adnan UA Kambhoh S Majeed AA Imran Frequency of CNS lesion in a Tertiary Care Hospital - A 5-year studyBiomedica20173348

16 

H Joshi S Awasthi S Dutta R Bharadwaj Histopathological spectrum of central nervous system lesionsTrop J Path Micro2019511844910.17511/jopm.2019.i11.02

17 

RR Kaki B Anuradha BS Rani Imaging of intracranial space occupying lesions-A prospective study in a tertiary care centreJ Evid Based Med Healthc20174116172310.18410/jebmh/2017/120

18 

PK Datta SR Sutradhar MNAA khan MZ Hossain SM Sumon I Hasan Clinical pattern of intra cranial space occupying lesion in tertiary level hospitalJ Dhaka Med Coll2019281172210.3329/jdmc.v28i1.45751

19 

SN Shashidhar T Teerthanath Clinicopathological study of central nervous system tumoursIndian J Basic Appl Med Res20176336170

20 

K Lakshmi M Hemalatha SB Sunkesula TDS Arasi LB Rao Histopathological Study of Spectrum of the Lesions of Central Nervous System in a Tertiary Care HospitalJ Evol Med Dent Sci201547114550

21 

R Thambi S Kandamuthan S Sainulabdeen L Vilasiniamma TR Abraham PK Balakrishnan Histopathological Analysis of Brain Tumours- A Seven Year Study from a Tertiary Care Centre in South IndiaJ Clin Diagn Res20171165810.7860/JCDR/2017/25623.9990

22 

SN Kanthikar DB Nikumbh ND Dravid Histopathological overview of central nervous system tumours in North Maharashtra, India: a single center studyIndian J Pathol Oncol201741804

23 

F Kothari A Shah Prospective study of intra cranial tumourSEAJCRR201403591832

24 

T Kakshapati RB Basnet B Pant D Gautam Histopathological analysis of central nervous system tumors; an observational studyJ Pathol Nepal2018813938

25 

KC Jat SP Vyas NA Bihari K Mehra Central nervous system tumors: a histopathological studyInt J Res Med Sci201645153945

26 

MB Priscilla PRDG Basina NC Parankusa RV Bhaskar Spectrum of Central Nervous System Tumors - A Four Year Study In A Tertiary Care Center IOSR-JDMS20181711714

27 

Sunila BN Kumarguru TS Vasan GV Manjunath Space occupying lesions of central nervous system: A radiological-histopathological correlation studyIndian J Pathol Oncol2018512027

28 

J Jaiswal AH Shastry A Ramesh YT Chickabasaviah A Arimappamagan V Santosh Spectrum of primary intracranial tumors at a tertiary care neurological institute: A hospital-based brain tumor registryNeurol India201664494501



jats-html.xsl


This is an Open Access (OA) journal, and articles are distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as appropriate credit is given and the new creations are licensed under the identical terms.

  • Article highlights
  • Article tables
  • Article images

Article History

Received : 11-03-2021

Accepted : 09-08-2021


View Article

PDF File   Full Text Article


Copyright permission

Get article permission for commercial use

Downlaod

PDF File   XML File   ePub File


Digital Object Identifier (DOI)

Article DOI

https://doi.org/10.18231/j.ijpo.2021.100


Article Metrics






Article Access statistics

Viewed: 11733

PDF Downloaded: 384