The present study was carried out in the Dept. Of Histopathology & Radiology, M. P. Shah medical college, Jamnagar, Gujarat state of India and cases were referred from Dept. of Orthopaedics. Of G. G. Hospital, M. P. Shah Medical College, Jamnagar.

Introduction

Lytic lesion of bone is a frequently found radiological presentation of patients seen in orthopedic practice. A spectrum of pathological lesions can be presented in this form from inflammatory to neoplastic conditions. The histopathologist is the final person to guide an orthopedic surgeon for the treatment of patients with lytic lesion. Lytic lesions of the bone are the most common radiological findings in various bone diseases including inflammatory and neoplastic lesions. In osteolytic lesions are present where the destructive processes outstrip the laying down of new bone. Lytic bone metastases must be greater than 1 cm and have destroyed 30-50% of the bone density in order to be seen by x-ray. [1] It is important to remember, however, that some benign processes such as osteomyelitis can mimic malignant tumours, and some malignant lesions such as metastases or myeloma, can mimic benign. It is difficult to determine radiologically with plain film imaging whether a lytic lesion is benign or malignant. It is more accurate to describe whether the process looks aggressive or nonaggressive. Pyogenic osteomyelitis is an acute inflammatory condition most commonly causedby staphylococcus aureus.[2] The osteolyticlesions of tuberculosis may closely mimic those due to multiple myeloma or secondary malignant deposits. [3] Neoplastic lesions, benign, malignant (primary and secondary) also produce lytic lesion in bones. Common presentations are progressive pain, swelling, tenderness & in some cases,acute pathological fracture. Within benign lesions, the differential diagnosis of lytic lesions includes simple bone cyst, aneurysmal bone cyst, osteochondroma (exostosis), enchondroma, giant cell tumor, fibrous dysplasia, osteoblastoma, chondroblastoma, non ossifying fibroma and brown tumour of the bone. Among the malignant tumors, the most common are primary bone tumors which include Ewing’s sarcoma, osteosarcoma, multiple myeloma and adamantinoma. Primary bone cancer is much rarer than bone metastasis.[4] Bone is the third most common site of metastatic disease.[5] 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. Carcinomas are much more likely to metastasize to bone than sarcomas. The axial skeleton is seeded more than the appendicular skeleton, partly due to the persistence of red bone marrow in the former. The ribs, pelvis and spine are normally the first bones involved and distal bones are rarely affected. Diagnosis of all lytic lesions is made by radiological modalities like plain X-ray, CT scan, MRI and bone scintigraphy.

Materials & methods

The study was carried out at departments of orthopedic, radiology and pathology.
The criteria for the selection of patient are cases of radiologically apparent bone disease.
Total seventy cases were selected and in all patients lytic lesion of bone was diagnosed
radiologically. In orthopedic OPD, patients clinically presented with pain, swelling, non healing
fracture. Detailed history was taken which mainly included age, sex, place of residence,
occupation, fever, weight loss, cough, haemoptysis or history suggestive of systemic
involvement. All patients were subjected to through physical examination both, systemic and
general examination.

In all patients X-ray of lesioned bone had been taken while CT scan and MRI were done
according to the need and advice of orthopedic surgeon. Pathological investigation included
routine CBC, ESR and Urine examination in all patients while sputum, body fluid examination,
Serum Calcium and alkaline phosphatase were done in selected cases.

Biopsy for histopathology was performed in all patients for the diagnosis of lytic lesions
of bone. Biopsy was taken mainly by scrapping method, 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 was 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. In selected cases IHC was performed to confirm histopathological findings.

Results

In results of our study 24 cases of inflammatory, 30 cases of benign, 6 cases of primary
malignant and 10 cases of secondary malignant lytic lesions were found out of total 70 cases. So,
the most common lytic lesion was benign neoplastic lesion of bone. (30 cases) [Table -1].

Figure 1

Table 1:Showing proportion of different lytic lesion.

Out of 70 patients, 46(65.71%) were male and 24(34.28%) were female. In male patients 20 cases were of benign neoplastic lesion, 14 cases were inflammatory lesion and 12 cases were malignant lesion. Where as in female, 10 cases were benign lesion, 10 cases were inflammatory lesion and 4 cases were malignant lesion. So, benign neoplastic lesions were the most common among both the sex. [Table- 2]. From different age group, the most common age group was 11-20 years, in which total 24 cases of lytic lesion were found, in which benign neoplastic lesions (18 cases) were most common. In age group 21-40 years, total 22 cases of lytic lesion were found, in which benign lesion (10 cases) was most common. In age group of above 40 years, total 22 cases of lytic lesion were found, in which 10 malignant lesions were found. In below 10 year group only 2 case found which was of malignant types. [Table-3].

Figure 2

Table 2: Gender distribution of the lytic lesions of bone.

Figure 3

Table 3: Age wise distribution of the lytic lesions of bone.

Out of total 24 inflammatory lytic lesions, 10 cases were of pyogenic osteomyelitis and 14 cases were of tuberculous osteomyelitis. So, tuberculous osteomyelitis was slightly more
common than pyogenic osteomyelitis in inflammatory lytic lesion.[Table-4].. From total 30
benign neoplastic lytic lesions, 16 cases were of giant cell tumor, 4 cases were of fibrous
dysplasia. Giant cell tumours show a higher incidence than other benign lytic lesion.[Table-5].

Figure 4

Table 4: Showing distribution of inflammatory lesion.

Figure 5

Table 5: Showing distribution of benign lesion.

While in 16 malignant lesions, 6 cases were primary and 10 cases were secondary malignant lesions. So, Secondary lesions were more common than primary in malignant lytic lesions.[Table-6].

Figure 6

Table 6: Showing distribution of malignant lytic lesion.

KEY HISTOPATHOLOGICAL FEATURES OF LYTIC LESION IN OUR STUDY
INFLAMMATORY LESIONS- In cases of pyogenic osteomyelitis large areas of
necrosis, focal area of hemorrhage and acute inflammatory cells are found. In cases of
tuberculous osteomyelitis, presence of epitheliod cells and caseation necrosis were inevitable.
Few langhans giant cells and evident granuloma could be seen.

BENIGN NEOPLASTIC LESION- Out of sixteen cases of giant cell tumour, ten cases
were from grade-I (conventional giant cell tumour), these tumours were showing many giant
cells with plenty of nuclei located in central with abundant cytoplasm. Four cases of giant cell
tumour were from grade-II, Two cases of giant cell tumour were having aggressive morphology
(grade-III) in which number of giant cells were too less, number of nuclei in giant cells were
less with atypical nuclear morphology and nuclei were arranged at the periphery of cell. Stromal
cells were having aggressive nuclear morphology. Four cases of fibrous dysplasia were showing
irregular, curvilinear bony trabeculae (Chinese letter pattern) lined by very few osteoblast in the
background of bland fibrous stroma. Two cases of chondroblastoma were showing sheets of
chondroblast having coffee-bean shaped nuclei along with chondroid matrix & giant cells. Two
cases of enchondroma were composed of hyaline cartilage containing bland appearing
chondrocytes. While simple bone cysts were showing cystic cavity lined by bland cell. In the two
cases of aneurysmal bone cysts, hemorrhagic cystic cavity surrounded by bland fibrous stroma
containing giant cell and reactive woven bone were seen. The two cases of langerhans cell histiocytosis showed plenty of eosinophils in the background of coffee bean shaped multilobated
histiocyte.

MALIGNANT LESION- Four cases of Ewing’s sarcoma were showing small blue round
cells having very scanty cytoplasm arrange in a sheets seperated by fibrovascular stroma. Two
cases of osteosarcoma showed lace like neoplastic osteoid formed by anaplastic osteoblast and
abnormal mitotic figure. Four cases of lung carcinoma metastasized to bone consisting of
squamous cell carcinoma shows pleomorphic squamous epithelial cells in the back ground of
bony trabeculae. Another two cases of adenocarcinoma of lung were showing malignant
columnar cell arranged in adenoid pattern, which were confirmed at higher centre by IHC,
tumours were positive for CEA and TTF-1. Two cases of secondaries were showing cells with
ground glass nuclei, nuclear groove and arranged in a classical follicular pattern & thick colloid
leads to diagnosis of follicular variant of papillary carcinoma in the clinically unsuspected cases
(fig-1). Two cases were showing lobular arrangement of clear cells separated by vascular
network leads to diagnosis of clear cell carcinoma of kidney, also confirmed at higher centre by
IHC, tumours were positive for CK-7 and vimentin.

Figure 7

Fig -1 Microphotograph of bony metastases in a case of Follicular variant of Papillary Carcninoma showing cells with ground glass nuclei, nuclear groove and arranged in a classical follicular pattern with thick colloid & bony trabeculae. (400 x,

Discussion

This study was carried out precisely to diagnose different lytic lesions of bone. 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; most cases after 25 years of age. Ewing's
sarcoma and simple bone cyst in the long bones of children and young teenagers, and giant cell
tumor in the young to middle-aged adult (20 to 50 years of age).[5,6] But in our study, maximum
number (10 out of 16) of cases were found in second decade only. Even the most common age
group of all lytic lesions was 11-20 years, in which total 24 cases of lytic lesions were found
composed of 18 cases of benign neoplastic lesions. In age group 21-40 years total 22 cases of
lytic lesion were found, in which benign (10 cases) were the commonest. In age group above 40
years, a total of 22 cases were found, in which malignant lytic lesion was the most common
diagnosis. In below 10 year group only 2 cases were found of Ewing’s sarcoma(fig-2).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.[7] The osteolytic lesions of tuberculosis at multiple sites need to be differentiated from multiple myeloma, secondary metastasis and bacterial osteomyelitis. Delay in diagnosis is usually due to the patients presenting late or it may be due to lack of awareness and its insidious onset.[8]

Figure 8

fig-2 Shows X-ray Lytic lesion of Ewing’s sarcoma at lower end of femur

Histopathological examination yields a high percentage of positive results.[9,10] In our
histopathological study, tuberculosis was more common than bacterial osteomyelitis in inflammatory lytic lesion and mostly found in elderly age groups. Ewing sarcoma and lymphoma
are important differential diagnoses.

In our study, out of 70 cases of lytic bone lesions, most common were benign neoplastic
lesions making 30 cases. Out of 30 benign neoplastic lytic lesions, 16 cases were giant cell
tumour of bone(fig-3). In present study, the most common site of giant cell tumor was lower end of femur and upper end of tibia. Giant cell tumor accounts for 5 to 9 percent of all primary bone
tumors. It is the most common bone tumor. Most patients present with slowly progressive pain,
with or without a mass. Symptoms arise when the lesion begins to destroy the cortex and irritate
the periosteum or when the weakening of the bone caused by the tumor causes pain due to
imminent pathologic fracture. Some giant cell tumors present with a pathologic fracture.
Radiological findings demonstrate the lesion is most often eccentrically placed to the long axis of
the bone.[11]

Figure 9

fig-3 Shows X-ray Lytic lesion of giant cell tumor at lower end of radius.

Other benign lytic lesions included 4 cases of fibrous dysplasia and in both cases site of
lesion was upper end of tibia. Langerhans cell histiocytosis usually presents as a pathological
fracture or an incidental finding and heals spontaneously.[7] In our study. Langerhans cell
histiocytosis was presented with pain and pathological fracture since 8 months in a 16 year male
patient which was previously diagnosed as acute on chronic osteromyelitis by another
pathologist and didn’t respond to treatment and after that referred to us. So careful
histopathological examination is required to differentiate osteomyelitis and langerhans cell
histiocytosis.

Ewing's sarcoma is found in the lower extremity more than the upper extremity, but any long tubular bone may be affected. The most common sites are the metaphysis and diaphysis of the femur followed by the tibia and humerus. In our study, out of 70 cases of lytic bone lesion,
most common primary malignant lesion was Ewing’s sarcoma, the four cases were found in
lower end of femur & tibia, below 20 years of age. Osteosarcoma can arise in any bone of the
body but majority originate in long bones of appendicular skeleton, especially the distal femur,
followed by the proximal tibia & proximal humerus- sites containing the most proliferative
growth plates. In the long bones the tumour is most frequently centered in the metaphysic (90%),
infrequently in the diaphysis (9%), and rarely in epiphysis.[12] In our study, two cases of
osteosarcoma were found in elderly male patients in lower end of femur which were confined to
metaphysis.

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.[13] 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. Hypercalcemia only occurs in 10% of patients.[14] In our study eight
cases of metastatic lytic lesion were found, which included Follicular Variant Of Papillary
Carcinoma of thyroid metastasize to upper end of femur, Carcinoma of kidney with metastasis to
L3 vertebra, Squamous Cell Carcinoma of lung and adenocarcinoma of Lung metastasize to
upper end of humerus. Six cases were presented with pain, weight loss and non healing
pathological fracture. All the eight cases had shown increase level of alkaline phosphatase while
adenocarcinoma of lung with metastasis to bone found to have hypercalcemia. In case of
follicular variant of papillary carcinoma of thyroid lytic lesion over upper end of femur were the
first noticeable sign and even the patient & clinician were unaware of thyroid malignancy.

Finally we conclude, 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.
Among the various diagnoses, benign tumors form the largest group (42.85%) of patients
presenting with a lytic lesion on radiological findings. There is a male preponderance with
65.71% of the patients being males. Also, majority of the patients fall into the second decade
with 34.28% 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, secondaries were a commoner diagnosis as opposed to the
primaries, and they tend to occur more commonly in the elderly population. The commonest
primary malignant lesion that showed up was Ewing’s sarcoma. 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 lytic lesions may have
osteoclastic giant cells and they should not be misinterpreted as Giant cell tumor.