Histomorphological Pattern of Radiologically Detected Osteolytic Lesions of Bone – A Study of Eighty Cases
*Runa NJ,1 Khan JB,2 Kaizer N,3 Dewan MR,4 Sharmin S,5 Ahmed SS,6 Hasan AM,7 Haque N,8 Hussain M9
Abstract:
To determine the spectrum of lesions and to correlate them with age, sex of patients and also anatomical site a histomorphological study of radiologically detected osteolytic lesions of bone was done. Eighty cases of radiologically detected lytic lesions of bone were studied over a period of two years from January 2014 to December 2015. Out of 80 cases of lytic lesion of bone, 18 cases were of inflammatory, 32 cases were of benign tumors, 20 cases of primary malignant bone tumors and 10 cases of metastatic lytic lesions were found. Most of the patients belonged to the middle age group with the age incidence varying with the type of lesion. Out of the 80 cases, 46 were males and 34 were females. Most of the bone diseases occurred more commonly around the knee joint and in the males within the age group of 11-20 years. Conclusion: Benign tumors are more common amongst all lytic lesions with giant cell tumor ranking first. Tuberculous osteomyelitis is more common in this study than pyogenic osteomyelitis. Osteosarcoma and secondary metastasis were more common among malignant bone tumors.
[Journal of Histopathology and Cytopathology, 2017 Jul; 1 (2):83-90]
Key words: Bone, Osteolytic lesions, Histopathology, Radiology
- *Dr. Nusrat Jahan Runa, Assistant Professor, Department of Pathology, Dhaka Central International Medical College, Dhaka. njruna03@gmail.com
- Zubaida Bahroon Khan, Lecturer, Department of Pathology, Dhaka Medical College, Dhaka.
- Nahid Kaizer, Assistant Professor of Pathology, MH Samorita Medical College, Dhaka.
- Md. Rezaul Karim Dewan, Professor of Pathology, Dhaka Medical College, Dhaka.
- Shegufta Sharmin, Resident of Pathology, Dhaka Medical College, Dhaka.
- Syed Salauddin Ahmed, Associate Professor of Pathology, National Institute of Traumatic and Orthopedic Rehabilitation, Dhaka.
- AZ Mahmudul Hasan, Assistant Registrar, Department of Orthopedic Surgery, Dhaka Medical College Hospital, Dhaka
- Nazmul Haque, Associate Professor, Department of Pathology, Dhaka Medical College, Dhaka.
- Maleeha Hussain, Professor and Head, Department of Pathology, Dhaka Medical College, Dhaka.
*For correspondence
Introduction
Lesion of bone is a frequently found radiological presentation of patients seen in orthopedic practice. Osteolytic lesions are evident radiologically where the destructive processes outstrip the laying down of new bone. The spectrum of pathological conditions causing osteolytic changes can be inflammatory to neoplastic lesions.1-3 Within benign lesions, the common differential diagnosis of lytic lesion includes simple bone cyst, aneurysmal bone cyst, osteochondroma (exostosis), enchondroma, non-ossifying fibroma and brown tumor of the bone. Among the malignant tumors the most common are Ewing sarcoma, osteosarcoma and multiple myeloma.4 Primary bone cancer is much rarer than bone metastasis.5,6 Bone is the third most common site of metastatic disease. Metastatic tumor that produces osteolytic lesions, detected in X-ray when the lesion is greater than 1.0 cm and 30% – 50% of the bone density have beendestroyed.4 As far as secondary tumors are concerned primary sites like lung, kidney, thyroid, breast, gastrointestinal and melanomas produce mainly lytic lesion while others elicit mixed lytic and sclerotic reaction.7 Carcinomas are much more likely to metastasize to bone than sarcomas.
It is difficult to determine radiologically with plain film imaging whether a lytic lesion is benign or malignant. It is important to remember, however that some benign processes such as osteomyelitis can mimic malignant tumors and some malignant lesions such as metastases or myeloma can mimic benign. The osteolytic lesions of tuberculosis may closely mimic those due to multiple myeloma or secondary malignant deposits.8 The histopathologist is the final person to guide an orthopedic surgeon for the treatment of patients with lytic lesions.
Methods
This study was conducted at the Department of Pathology, Dhaka Medical College, Dhaka from January 2014 to December 2015. The criterion for the selection of the patient was radiologically detected osteolytic lesions of bone. Total 80 cases were selected. Detailed history was taken. Biopsy for histopathology was performed in all patients for the diagnosis of lytic lesions of bone. Biopsy was taken mainly by incision and excision method.
In laboratory soft tissue were fixed in 10 % formalin while for bone 3 to 5 mm thick sections were made and adequately fixed in 10% buffered formalin and then decalcification was achieved by placing the specimens in 5% nitric acid for 2 days. After that all tissue were processed by increasing concentrations of alcohol and paraffin blocks were prepared. Sectioned were stained with haematoxylin and eosin. After that all slides were examined under microscope, the final diagnosis was made into inflammatory, benign and malignant lesion accordingly.
Results
In this study 18 cases of inflammatory, 32 cases of benign, 20 cases of primary malignant and 10 cases of secondary malignant lytic lesions were found out of total 80 cases. Benign neoplastic lesions of bone comprises the highest number (32 cases, Table I).
Table I: Distribution of frequency of study patients by histological diagnosis (n=80)
| Lesions | Number | % |
| Inflammatory | 18 | 22.5 |
| Neoplasm | ||
| Benign | 32 | 22.5 |
| Malignant primary | 20 | 25.0 |
| Malignant Secondary | 10 | 12.5 |
| Total | 80 | 100% |
From different age group, the most common age group was 11-20 years, in which total 32 cases of lytic lesion were found. Benign neoplastic lesions (18 cases) were most common in this group. In age group 21-40 years, total 25 cases of lytic lesion were found, of which benign lesion (12 cases) was most common. In age group of above 40 years, total 19 cases of lytic lesion were found, in which 12 malignant lesions were found. In below 10 year group only 4 cases were found, which were of malignant type (Table II).
Table II: Showing distribution of the study patients by age
|
Lesions |
Age groups (in years) | ||||
| 0-10 | 11-20 | 21-40 | Above 40 | ||
| Inflammatory | Pyogenic Osteomyelitis | 0 | 4 | 2 | 2 |
| Tuberculous osteomyelitis | 0 | 1 | 6 | 3 | |
| Neoplasm | Benign | 0 | 18 | 12 | 2 |
| Malignant primary | 4 | 9 | 3 | 4 | |
| Malignant secondary | 0 | 0 | 2 | 8 | |
| Total | 4 | 32 | 25 | 19 | |
Out of 80 patients, 46 (57.50%) were male and 34 (42.50%) were female. In male patients 19 cases were of benign neoplastic lesion, 8 cases were inflammatory lesion and 19 cases were malignant lesion. Where as in female, 13 cases were benign lesion, 10 cases were inflammatory lesion and 11 cases were malignant lesion. So, benign neoplastic lesions were the most common among both the sex (Table- III).
Table III: Types of leions with sex distribution of the study patients
| Lesions | Male | Female | |
| Inflammatory | Pyogenic osteomyelitis | 02 (2.5%) | 06 (7.5%) |
| Tuberculous osteomyelitis | 06 (7.5%) | 04 (5.0%) | |
|
Benign |
Giant cell tumor | 06 (7.5%) | 09 (11.25%) |
| Enchondroma | 04 (3.75%) | 01 (1.25%) | |
| Simple bone cyst | 02 (2.5%) | 01 (1.25%) | |
| Fibrous dysplasia | 02 (2.5%) | 01 (1.25%) | |
| Aneurymal bone cyst | 03 (3.75%) | 01 (1.25%) | |
| Hemangioma | 02 (1.25%) | — | |
|
Malignant |
Primary | ||
| Osteosarcoma | 05 (6.25%) | 03 (3.75%) | |
| Ewing sarcoma | 03 (3.75%) | 04 (5.0%) | |
| Chondrosarcoma | 02 (2.5%) | 01 (1.25%) | |
| Multiple myeloma | 01 (1.25%) | — | |
| MFH | 01 (1.25%) | — | |
| Secondary | 07 (8.75%) | 03 (3.75%) | |
| Total | 46 (57.50%) | 34 (42.50%) | |
Out of 80 cases, 24 patients had osteolytic lesion in the tibia. Among them 17 lesions were in the upper end. The second most common site of lesion was femur [Table IV].
Table IV: Distribution of the study patients according to anatomical site (n=80)
| Diagnosis | Femur Upper |
Femur
Lower |
Tibia
Upper |
Tibia
Lower |
Fibula | Humerus | Radius | Meta-carpal | Phalanges | Total |
| Tubercular osteomyelitis | – | 2 | 3 | 3 | – | – | – | 1 | 1 | 10 |
| Pyogenic osteomyelitis | – | 2 | 2 | 2 | – | 1 | 1 | – | – | 8 |
| Giant cell tumour of bone | – | 6 | 3 | 2 | 1 | 1 | 1 | – | – | 15 |
| Enchondroma | – | – | – | – | – | – | – | 1 | 4 | 5 |
| Hemangioma | – | – | – | – | 1 | 1 | – | – | – | 2 |
| Benign cystic lesion | – | – | – | – | 1 | 1 | 1 | – | – | 3 |
| Aneurysmal bone cyst | – | – | 1 | 1 | – | 2 | – | – | – | 4 |
| Fibrous dysplasia | – | – | 2 | 1 | – | – | – | – | – | 3 |
| Ewing sarcoma | 1 | 2 | 1 | – | 1 | 1 | 1 | – | – | 7 |
| Osteosarcoma | 3 | 5 | – | – | – | – | – | – | 8 | |
| Chondrosarcoma | 1 | – | – | – | – | 2 | – | – | – | 3 |
| Multiple myeloma | 1 | – | – | – | – | – | – | – | – | 1 |
| MFH | – | 1 | – | – | – | – | – | – | 1 | |
| Metastatic adenocarcinoma | – | – | 1 | – | 2 | – | – | – | 3 | |
| Metastatic squamous cell carcinoma | 1 | – | – | – | – | – | – | – | – | 1 |
| Metastatic renal cell carcinoma | 2 | – | – | – | – | – | – | – | – | 2 |
| Metastatic follicular variant of papillary carcinoma | – | – | – | – | 2 | 1 | – | – | 3 | |
| Metastatic Prostatic carcinoma | 1 | – | – | – | – | – | – | – | – | 1 |
| Total | 6 | 15 | 18 | 10 | 4 | 14 | 5 | 2 | 5 | 80 |
MFH – Malignant fibrous histiocytoma
Out of total 18 inflammatory lytic lesions, 8 cases were of pyogenic osteomyelitis and 10 cases were of tuberculous osteomyelitis (fig 1 and 2). So, tuberculous osteomyelitis was slightly more common than pyogenic osteomyelitis in inflammatory lytic lesions (Table V). From total 32 benign neoplastic lytic lesions, 15 cases were of giant cell tumor, 5 cases were of enchondroma. Giant cell tumour shows a higher incidence than other benign lytic lesion (Table VI).
Table V: Distribution of inflammatory lesion
| Histologically diagnosed Inflammatory lesion | Number | % |
| Pyogenic osteomyelitis | 08 | 10 |
| Tuberculous osteomyelitis | 10 | 12.5 |
Table VI: Distribution of frequency of benign lesion by histopathological diagnosis
| Histologically diagnosed Benign lesion | No of cases | % |
| Giant cell tumor | 15 | 18.75 |
| Enchondroma | 05 | 6.25 |
| Simple bone cyst | 03 | 3.75 |
| Fibrous dysplasia | 03 | 3.75 |
| Aneurysmal bone cyst | 04 | 5.0 |
| Hemangioma | 02 | 2.5 |
| Total | 32 | 40.0 |
While in 30 malignant lesions, 20 cases were primary and 10 cases were secondary malignant lesions. Primary malignant lesions were more common than metastatic lytic lesions in the present series (Table VII).
Table VII: Distribution of frequency malignant lytic lesion by histological diagnosis
| Malignant lesion | No of cases | Percentage (%) | |
| Primary | Osteosarcoma | 08 | 10 |
| Ewing sarcoma | 07 | 8.75 | |
| Chondrosarcoma | 03 | 3.75 | |
| Multiple myeloma | 01 | 1.25 | |
| Malignant fibrous histiocytoma | 01 | 1.25 | |
| Secondary | Metastatic follicular variant of papillary carcinoma of thyroid in bone |
03 | 3.75 |
| Metastatic adenocarcinoma of lung in bone | 03 | 3.75 | |
| Metastatic renal cell carcinoma in bone | 02 | 2.5 | |
| Metastatic adenocarcinoma of prostate in bone | 01 | 1.25 | |
| Metastatic squamous cell carcinoma of lung in bone | 01 | 1.25 | |
| Total | 30 | 37.5 | |
Osteosarcoma and metastatic tumours from lung were common in the primary and secondary malignant tumour groups (fig 3 and 4).
Fig 1. X-Ray photograph showing lytic area in the right upper tibia. Subsequent biopsy revealed tubercular osteomyelitis (case no 16)
Fig 2. Photomicrograph of the case in fig 1 showing epithelioid cells, lymphocytes, a giant cell and bone, consistent with tubercular osteomyelitis (ase No: 16, H & E stain ´200)
Fig 3. X-ray photograph showing lytic lesion with destruction of the overlying cortical bone with ‘sunburst’ appearance in lower end of femur (Case no. 42)
Fig 4. Photomicrograph showing Osteosarcoma (Case No: 42, H&E stain ´400)
Fig 5. X-ray photograph showing a lytic lesion in upper end of femur (Case no. 17)
Fig 6. Photomicrograph showing metastatic squamous cell carcinoma (Case No: 17, H&E stain´400)
Discussion
This study was carried out to determine various histomorphologic pattern of lytic lesions of bone. Of total 80 cases, 18 cases of inflammatory, 32 cases of benign neoplastic lesion, 20 cases of primary malignant bone tumors and 10 cases of secondary tumors were found. One of the important point to be considered is the age of the patient. Some of the lytic lesions are most probably confined to certain age groups such as: metastatic neuroblastoma in the infant and young child, metastasis and multiple myeloma in the middle-aged and elderly, lymphomas affecting only bone usually occur during adult life. Ewing sarcoma mostly affecting children and young teenagers while giant cell tumor in the young to middle aged adults.9,10 In our study, the most common age group of bone lesions was in second decade. Among 32 cases of benign osteolytic lesion, 18 cases were belonging to age group 11-20 years. In age group 21-40 years, total 25 cases of lytic lesion were found, in which benign (12 cases) were the commonest. In age group above 40
years, a total of 19 cases were found, in which malignant lesion was the most common diagnosis. In below 10 years age group only 4 cases were found to be Ewing’s sarcoma (Table II).In our study, osteomyelitis was found in all age groups above ten years. The diagnosis of chronic recurrent multifocal osteomyelitis is essentially one of exclusion. Infective osteomyelitis and malignancy are the main differential diagnoses.11 The osteolytic lesions of tuberculosis at multiple sites need to be differentiated from multiple myeloma, secondary metastasis and bacterial osteomyelitis.
In this study, more than half (57.50%) of the patients were male and 42.50% were female; male to female ratio was 1.4:1, which indicates that osteolytic lesion are predominant in male subjects, which closely agrees with available literature.12,13
The bone around the knee joint that is, the distal end of the femur and the proximal end of the tibia, were found to be the commonest sites for osteolytic lesions comprising 38.7% in this series. The lower end of the femur was affected in 17.5% of cases and the upper end of the tibia in 21.2% of cases that has matched with other literature.14
In our study, out of 80 cases of lytic bone lesions, most common were benign neoplastic lesions making 32 cases. Among them, 15 cases were giant cell tumour of bone having female predominance (Table III). In present study, the most common site of giant cell tumor was lower end of femur and upper end of tibia [Table IV]. Characteristic radiologic findings demonstrate the lesion is most often eccentrically placed lytic lesion with no periosteal reaction to the long axis of the bone. Total 5 cases of enchondroma has been reported with an incidence of 6.26% of total cases and an incidence of 15% of all benign tumors, mostly seen in patients younger than age 20 years (3/5 cases) in the current study.
Osteosarcoma is the most common primary bone tumor in young and adolescents. It occurs most frequently in the second decade, occurring in the metaphysis, mostly in lower end of femur followed by upper end of tibia.15,16 In the present study, we observed a similar finding. Ewing sarcoma is a highly malignant, undifferentiated, peripheral primitive neuro-ectodermal tumor occurring most commonly at the diaphysis of long bones, in the 0-20 years age group, with female predominance.15,16 Our study has matched with the available literature. Pain, pathological fractures and hypercalcemia are the major sources of morbidity with bone metastasis. Pain is the most common symptom found in 70% patients with bone metastases.17 Pain is caused by stretching of the periosteum by the tumor as well as nerve stimulation in the endosteum. Pathological fractures are most common in breast cancer due to the lytic nature of the lesions.18 In our study ten cases of metastatic lytic lesion were found, which included Follicular Variant Of Papillary Carcinoma of thyroid metastasize to upper end of the humerus, Carcinoma of kidney with metastasis to upper end of femur, Squamous Cell Carcinoma and adenocarcinoma of Lung metastasize to upper end of femur and humerus. In case of follicular variant of papillary carcinoma of thyroid lytic lesion over humerus was the first noticeable sign and even the patient & clinician were unaware of thyroid malignancy.
Among the various diagnoses, benign tumors form the largest group (40%) of patients presenting with a lytic lesion on radiological findings. There is a male preponderance with 57.5% of the patients being males. Also, majority of the patients fall into the second decade with 40% of the patients in the age group of 11- 20 years. The common diagnoses among the benign lesions were giant cell tumors, while there were a slightly higher number of cases of tuberculous osteomyelitis as against bacterial osteomyelitis in the inflammatory conditions. Among the malignant lesions, primary tumors were a commoner diagnosis as opposed to the secondaries. The metastatic tumors tend to occur more commonly in the elderly population. The commonest primary malignant lesion that showed up was osteosarcoma. Overall, giant cell tumor is the commonest diagnosis presenting with a lytic lesion on radiological finding. Occult malignancy can be presented as lytic lesion of bone in the form of secondary. All lyticlesions may have osteoclastic giant cells and they should not be misinterpreted as Giant cell tumor.
Conclusion
Lytic lesion of bone is a very used to radiological finding for orthopedic surgeon in many patients. Even an orthopedic surgeon and radiologist together won’t be able to reach to the precise conclusion and further treatment. Histopathology is the gold standard for the precise diagnosis from a very large number of conditions leading to lytic lesion.
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