# Primary Malignant Tumours of Bone Following Previous Malignancy

Authors: J. T. Patton; S. M. M. Sommerville; R. J. Grimer
Journal: Sarcoma
 (2008)

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## Abstract

Destructive bone lesions occurring in patients who have previously had a malignancy are generally assumed to be a metastasis from that malignancy. We reviewed  60 patients with a previous history of malignancy, who presented with a solitary bone lesion that was subsequently found to be a new and different primary sarcoma of bone. These second malignancies occurred in three distinct groups of patients: (1) patients with original tumours well known to be associated with second malignancies (5%); (2) patients whose second malignancies were likely to be due to the previous treatment of their primary malignancy (40%); (3) patients in whom there was no clearly defined association between malignancies (55%). The purpose of this study is to emphasise the necessity for caution in assuming the diagnosis of a metastasis when a solitary bone lesion is identified following a prior malignancy. Inappropriate biopsy and treatment of primary bone sarcomas compromises limb salvage surgery and can affect patient mortality.


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## Body

## 1. Introduction

With the advances in the treatment of many cancers, patient
survival has improved dramatically such that a second malignant neoplasm is now
observed more frequently [1, 2]. It is well known that certain
cancers are associated with an increased risk of a second cancer [3, 4], and
that some treatments for cancer are in themselves known to be aetiological
agents in the pathogenesis of a second cancer [5, 6] . It is commonly
assumed that bone lesions occurring in patients who have already had a
malignant neoplasm are metastases from that malignancy. If the lesions are multiple, this will almost
always be true, but if the lesion is solitary then further investigation is
necessary to exclude other pathologies such as another primary bone tumour.


## 2. Materials and Methods

The patients for this study were identified from a
prospectively recorded database. The records of 60 patients who presented to
our institution between 1980 and 2001 with a primary bone tumour following a
prior malignancy were reviewed. The data was analysed in three separate groups,
although it should be pointed out that certain patients might belong to more
than one group.Group 1
Patients were categorised into this
group if they had a primary malignant neoplasm that is known to have a strong
relationship with the development of a secondary malignancy.Group 2
This group included patients who had
treatment of their primary tumour that is known to predispose to the
development of secondary sarcoma. This includes all the radiation-induced
sarcomas that arose within the radiation field.Group3
Patients who developed a primary
tumour of bone, subsequent to a different primary malignant neoplasm that was
not clearly related to that neoplasm or to the treatment used for that
neoplasm, were included in this group.


## 3. Results

At latest follow up, 31 patients (52%) within the study group had died of disease relating to the primary bone
sarcoma. The average time to development of metastases was 17.6 months (range 0–122 months).Group 1
This group consisted of three patients (5%),
all of whom had retinoblastoma as their first tumour. The sarcoma that subsequently
developed was an osteosarcoma in two and a primary leiomyosarcoma of bone in
the other. The ages at which the second tumour arose were ten, sixteen, and
twenty three years, with a lag time from the original tumour of eight, fifteen,
and twenty two years, respectively. All the second tumours were located in
sites remote from the head and neck.Group 2
There were twenty four patients (40%) who
developed a sarcoma following previous radiotherapy for a primary tumour. Of
these, twenty two were osteosarcoma and two were high-grade sarcoma with no
identifiable differentiation. All of these secondary tumours were located in
the previous radiation field. The average age of the patients at time of
diagnosis of the second tumour was 45 years (range 16–80 years) with a lag time from the initial
tumour of 14 years (range 4–31 years).Group 3
Thirty three patients (55%) developed a primary
malignant bone tumour following a previous malignancy that was not felt to be
clearly related to or associated with the treatment of the first malignancy
(Table1). The average age at diagnosis of the second malignancy was 52 years
(range 8–84 years) and the
lag time between tumours was 5 years (range 0–18 years). The most common initial malignancy
was carcinoma of the breast (thirteen patients), which was associated with
chondrosarcoma in six cases. Three patients presenting with breast cancer
developed bone sarcomas in the proximal limb girdle. Only one of these patients
received radiotherapy as treatment for their breast cancer. The bone sarcoma in
this patient occurred in the contralateral proximal humerus. Chondrosarcoma was
the most common second malignancy, affecting twelve patients. The tumours
occurred at a wide distribution of sites, most frequently in the proximal femur
(eight patients). Three of the 33 patients presented with a soft tissue sarcoma
as the initial malignancy. The subsequent primary bone tumours were located in
sites remote from the initial sarcoma and were felt to have histology unrelated
to the initial tumour.Table 1
Data for the Group 3 patients, in whom there was no clearly defined
association between malignancies.
PatientAge (at diagnosis of second tumour)yrsSexSecond tumour (primary bone sarcoma)Initial malignancy (Ca: carcinoma)Site of second tumourLag (time to second tumour)yrs172FChondrosarcomaCa breastProx
femur14259FChondrosarcomaCa breastProx
humerus1350FChondrosarcomaCa breastProx
femur16458FChondrosarcomaCa breastProx
humerus2560FChondrosarcomaCa breastDistal
femur0660FChondrosarcomaCa
bronchusProx tibia2772FChondrosarcomaCa colonDistal
femur4844MChondrosarcomaCa
oesophagusPelvis6958MChondrosarcomaCa
rectumProx
tibia71082MChondrosarcomaLeukaemiaProx femur61152FChondrosarcomaMalignant
melanomaPelvis31266FChondrosarcomaCa breastMetatarsal01366FChordomaCa breastSacrum01455FChordomaCa breastSacrum121529FEwings
sarcomaCa kidneyProx femur01612FEwings
sarcomaHodgkin’s
lymphomaFibula6179MEwings
sarcomaLeukaemiaProx
tibia51878MFibrosarcomaMalignant
fibrous histiocytoma (soft tisssue)Pelvis21941FFibrosarcomaMalignant
melanomaProx
femur32084FLeiomyosarcomaCa breastDistal
fibula82147FMalignant
fibrous histiocytomaHodgkin’s
lymphomaDistal
femur62239MMalignant
fibrous histiocytomaSeminomaDistal
femur102327FMalignant
fibrous histiocytomaCa
breastProx
femur22466MOsteosarcomaCa bladderScapula32563FOsteosarcomaCa breastProx femur52610MOsteosarcomaHodgkin’s
lymphomaProx
humerus32733FOsteosarcomaMalignant
melanomaProx
tibia4288FOsteosarcomaRhabdomyosarcomaProx tibia52912MOsteosarcomaRhabdomyosarcomaProx
femur113081FSarcomaCa breastProx
fibula03172FSarcomaCa breastScapula33269MSpindle
cell sarcomaCa
prostateScapula13381FSpindle
cell sarcomaCa
colonProx
tibia18


## 4. Discussion

Significant progress has been made in the
treatment of and survival from numerous malignant neoplasms in recent years.
The improvement in patient survival has revealed previously unrecognised
sequelae. The second malignant neoplasm is a well-described entity [1, 2]. It
is becoming clearer that genetic factors play a major role in the aetiology of
the second malignant neoplasm. These factors are already well established in
patients with tumours such as retinoblastoma and Ewings sarcoma [4, 7]. In this
study, we have reported six cases of breast carcinoma associated with
chondrosarcoma. Recently, this association has been reported by others and a
genetic trait postulated [8]. It has also been observed that cancer patients
themselves are at greater risk of developing a subsequent malignancy than the
general population [1].Treatments for cancer have also been implicated in the
aetiology of a second malignant neoplasm. Radiotherapy is a well-established
causative agent and is dose dependent [6]. More recently, certain
chemotherapeutic agents have also been implicated [9].There is a tendency to assume that a solitary bone lesion
following a malignancy is a metastasis from that malignancy. This is especially
true if the patient is over 40 [10] , and the interval between the initial
malignancy and the second presentation is short. It was unfortunately beyond
the capability of this study to provide a denominator of the number of patients
with metastatic solitary bone lesions from the same population that presented
to our tertiary referral centre with second and different primary bone tumours.It is sobering to see that for the Group 3, patients in this
study the average interval between tumours was only five years, and the average
age of the patients was 52 years. In patients who have had radiotherapy to a
previous lesion (Group 2), the assumption that the subsequent bone lesion is
recurrent disease from the first malignancy can result in incorrect or
substandard therapy.The potential deleterious effects of a poorly performed
biopsy have been well described by Mankin et al. [11] . There are now several
reports illustrating the disastrous effects of inappropriate treatment of
primary bone sarcomas, usually
brought about by the assumption that the lesion is a metastasis [12]. In this
study, patients managed in our tertiary referral centre had a
biopsy prior to initial treatment. However, we know of at least 3 cases where
presumption of the diagnosis of metastasis led to substandard treatment. This
was caused by the assumption that the lesion was a metastasis, and the failure by
the general orthopaedic surgeon to maintain an index of suspicion that a
solitary bone lesion could be a primary bone sarcoma. Whist no particular traits were
established, lesions in atypical sites (e.g., scapula, fibula) should be
regarded with extrasuspicion. Most of the lesions in this study had characteristic
appearances of primary bone sarcomas rather than metastases.Internal fixation of these lesions can spread tumour cells
along the whole length of the bone, rendering limb salvage surgery impossible.
Clearly, therefore, we would urge caution in the treatment of solitary bone
lesions, even in the presence of previous malignancy. There is rarely error in
temporarily delaying potentially deleterious surgery or radiotherapy, imaging
the patient appropriately, and performing a biopsy by a surgeon experienced in
orthopaedic oncological procedure [13].



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