Bone metastases: A 

compilation of 365 histologically

Original Article

verified cases spanning over two decades from a single

center
Monalisa Hui, B. Balu, Shantveer G. Uppin, Megha S. Uppin, P. Chandrasekhar1, K. Nageshwara Rao1,
Suchanda Bhattarcharjee2, M. VijayaSaradhi2, Y. Vamshi Krishna2
Departments of Pathology, 1Orthopaedics and 2Neurosurgery, Nizam’s Institute of Medical Sciences, Hyderabad, Telangana, India

Address for correspondence:

Dr, Shantveer G. Uppin, Department of Pathology, Nizam’s Institute of Medical Sciences, Punjagutta, Hyderabad ‑ 500 082, Telangana,
India. E‑mail: drsguppin@yahoo.co.in

ABSTRACT Access this article online

Website: www.ijpmonline.org
Objective: To analyze the clinicopathological features of metastatic bone PMID: xxxxxxxxx (when available)
tumors over a period of two decades and identify the primary site of malignancy DOI: 10.4103/IJPM.IJPM_1132_20
in metastasis of unknown origin. Materials and Methods: A total number of Quick Response Code:
365 cases were included in the study. The clinical features and location of the
tumors were noted. The histopathological features of all the cases were studied.
Immunohistochemistry (IHC) was done either to categorize or confirm the primary
diagnosis using organ specific/organ restricted markers. Results: A total 712 bony
sites were involved by metastasis in 365 patients, of which spine was the most
commonly affected. Metastasis was the initial presentation in 69.5% patients. The
primary site was known in 220 patients and almost half of them were detected
after the diagnosis of metastasis. IHC was used as adjunct to suggest the
possible origin in cases with unknown primary in 27.4%. Among the metastatic
carcinoma, adenocarcinoma was the most common histological subtype with Imaging studies provide valuable
thyroid being the most frequent primary site of origin followed by lung and diagnostic information to the pathologist
breast. Conclusion: More than two‑third of cases in surgical pathology practice in skeletal metastasis. Conventional
present as initial manifestations. Detection rate of primary depends on extent X‑ray techniques as the initial imaging
of metastatic work‑up and IHC with organ specific/organ restricted markers to
modality lack sensitivity as 50–70% of
facilitate treatment with bone targeting agents.
bone destruction or lesions of more than
1.5 cm is required to demonstrate a change
KEY WORDS: Bone, metastases, secondaries
Submitted: 14-Sep-2020
Revised: 05-Oct-2020
INTRODUCTION Accepted: 06-Dec-2020
Published: 20-Oct-2021
Metastatic cancer is the most common malignant tumor affecting the skeleton.[1] After
lung and liver, skeletal system is the third most common site of metastases. The overall This is an open access journal, and
articles are distributed under the
incidence of bone metastases in cancer is approximately 30%. It may present either as terms of the Creative Commons
initial manifestation or may be sole manifestation in malignancy with unknown origin.[2] Attribution‑NonCommercial‑ShareAlike 4.0
Although any malignant tumor can metastasize to the skeleton, majority of them are License, which allows others to remix, tweak,
and build upon the work non‑commercially,
epithelial and originate from breast, prostate, lung, thyroid, and kidney.[3‑5] In children, as long as appropriate credit is given and
metastatic malignancies involving the bone includes neuroblastoma, Ewings sarcoma, the new creations are licensed under the
identical terms.
rhabdomyosarcoma, teratocarcinoma, and Wilm’s tumor.[6]
For reprints contact: WKHLRPMedknow_
reprints@wolterskluwer.com
Routine investigations are non‑specific. Apart from alkaline phosphatase which is
elevated in more than 50% of cases, SGOT, LDH, and uric acids are higher in patients
How to cite this article: Hui M, Balu B, Uppin SG,
with bone metastasis. The tumor markers like carcinoembryonic antigen (CEA), Uppin MS, Chandrasekhar P, Rao KN, et al. Bone
alpha‑fetoprotein (AFP), carbohydrate antigens (CA 15‑3, CA 19‑9, CA125), metastases: A compilation of 365 histologically
verified cases spanning over two decades
prostate‑specific antigen (PSA), tissue polypeptide antigen (TPA) have been shown to from a single center. Indian J Pathol Microbiol
be diagnostically nonspecific.[7] 2021;64:717-24.

© 2021 Indian Journal of Pathology and Microbiology | Published by Wolters Kluwer - Medknow 717
 Hui, et al.: Bone metastases
on routine study.[5,8‑10] Bone scan is more sensitive test but lacks
specificity.[4] Hence pathological examination is essential to
establish the diagnosis. It not only provides diagnosis but also is
helpful in suggesting possible primary if previously unknown.
In this study, the clinicopathological features of metastatic bone
tumors spanning over a period of two decades were analyzed and
an attempt was made to identify the primary site of malignancy
in metastasis of unknown origin.
MATERIALS AND METHODS
All histologically documented cases of metastatic bone tumors
diagnosed over a period of 20 years from January 2000 to
December 2019 were included in the study. The primary bone
tumors and hematolymphoid malignancies were excluded from
the study. This was a retrospective observational study and the
study was approved by the Institutional Ethics Committee.
The demographic data, clinical details, tumor markers, and
imaging findings were retrieved from the medical records.
Curetted material and resected specimens from suspected cases
of bone metastasis was processed for routine paraffin sections
after fixation in 10% buffered formalin. Decalcification was
carried out with 10% nitric acid whenever necessary prior to
processing. In addition to routine hematoxylin‑eosin stain,
special stains such as Alcian‑PAS were carried out wherever
necessary. Immunohistochemistry (IHC) was done either to
categorize or confirm the primary diagnosis. The panel of
immunohistochemical markers varied depending on the clinical
features and morphology of the tumors. A panel of CK7, CK20,
and organ specific/organ restricted markers were performed in
metastatic carcinoma to suggest or confirm the primary origin
of metastasis. The patients were divided into two groups based
on the information regarding the primary site. Group I included
patients with known primary and Group II included patients
with unknown primary. The Group I was further subdivided
into Group IA and Group IB depending on whether the primary
was known prior to or detected after the diagnosis of metastatic
disease, respectively. Group II was divided into Group IIA,
where the primary remained occult even after metastatic
work‑up and Group IIB where work‑up was not done or details
not available.
RESULTS
Of the total 365 cases of metastatic tumors involving the bone, the
age of the patients ranged from 3 to 90 years (median, 53 years)
with a male to female ratio of 1.2:1. Majority of the patients were
between fifth to seventh decades of life. The two youngest patients
were 3‑year‑old males with metastatic involvement of femur and
pelvis from adrenal neuroblastoma.
Pain was the single most common presenting complaint noted in
227 patients. The patients with spinal involvement presented with
weakness in limbs, paresthesia, bladder, and bowel disturbances.
Pathological fracture was noted in 74 patients.
718 I n d i a n J o u r n a l of Pathology and Microbiology ¦ Volume 64 ¦ Issue 4 ¦ October-December 2021
Skeletal distribution
A total 712 bony sites were involved by metastasis in 365 patients
under study. The number of metastatic sites per individual ranged
from 1 to 14 (average, >2 sites/patient). The distribution of the
affected skeletal sites are summarized in Figure 1. The axial
skeleton was more commonly involved than the appendicular
skeleton, of which spine was the most frequent site was biopsied
in the present study accounting for 190 cases (52.1%). Majority
of the cases involving the spine affected the thoraco‑lumbar
segment (146/190). In the appendicular skeleton, metastases were
uncommon beyond knee and elbow joint. None of our patients had
acral metastases. Other visceral organs concomitantly involved
were lung (10 patients), liver (4 patients), brain (4 patients),
and adrenal (2 patients).
Radiographic features
Plain radiographs were available in 65 patients, CT scan in
69 patients and MRI in 94 patients. Majority of the patients
showed mixed osteolytic and osteosclerotic lesions (69%)
followed by osteolytic lesions (29%) with only few showing
osteosclerosis (9%). Bone scan findings were available in
59 patients and were helpful in detecting the multiple sites.
Apart from metastasis, a differential diagnosis of giant cell
tumor, osteomyelitis, tuberculosis, neurofibroma, chondroid
lesion, osteosarcoma, and round cell tumor were considered on
imaging. The imaging findings of patients from various sites are
depicted in Figure 2.
Histological features
Initially the metastases were broadly categorized into carcinomas
and non‑epithelial malignancies/sarcomas. The distribution and
IHC of metastatic carcinomas with known primary is summarized
in Table 1. Of the metastatic carcinomas, adenocarcinoma
was the most common histological subtype accounting for
190 cases (52%). The others included poorly differentiated
carcinoma (41), thyroid carcinoma (60), renal cell carcinoma (23),
and squamous cell carcinoma (22). There were two cases each
of small cell carcinoma lung, adenosquamous carcinoma,
Figure 1: Distribution of skeletal metastasis. The numbers within the
parenthesis indicate non‑histologically verified sites evident on imaging
 Hui, et al.: Bone metastases

a b c

d e f g

h i j
Figure 2: Representative images of (a) osteolytic lesion involving the spine causing wedge compression. (b) Expansile osteolytic lesion involving
the right femur. (c) Involvement of the humerus with pathological fracture. (d and e) Expansile osteosclerotic lesion involving the skull (f and g)
Lytic lesion in mandible (h and i) Metastatic neuroblstoma involving proximal femur and tibia. (j) Expansile lytic lesion in the proximal humerus
in metastatic paraganglioma

and sarcomatoid carcinoma, one case each of hepatocellular
carcinoma, acinic cell carcinoma of the salivary gland, and a
single case of adenocarcinoma arising in a testicular teratoma
metastatic to spine. The non‑epithelial tumors metastasizing to
the bone are summarized in Table 2. These primarily comprised
of neuroblastoma, osteosarcoma, and Ewings sarcoma.
Classification of cases
Metastasis was the initial presentation in majority of the
patients (254, 69.5%) in the present study. The primary site was
known in 220 patients with almost half of them being detected
after the diagnosis of metastasis. The distribution of cases in
various groups are shown in Table 3. Thyroid was the most
common primary site followed by lung, breast, kidney, and
prostate. Most of the thyroid, lung, and renal cell carcinomas
presented with metastasis at initial diagnosis. In contrast majority
of the breast carcinomas were primarily diagnosed prior to
metastasis.
Indian Journal of Pathology and M i c r o b i o l o g y ¦ V o l u m e 6 4 ¦ I s s u e 4 ¦ O c t o b e r - D e c e m b e r 2 0 2 1 719
Among the 60 metastatic thyroid carcinomas, 45 were follicular
carcinoma, 11 conventional papillary carcinoma, and 3 follicular
variant of papillary carcinoma. Of these, 44 patients presented
initially with metastasis. IHC with CK7 TTF1 and thyroglobulin
confirmed the diagnosis in 13 cases. Rests of the cases were
diagnosed based on morphology in correlation with imaging
findings. There was one case of medullary thyroid carcinoma
who presented with lytic lesion in the C7 vertebrae on plain
radiograph and PET scan. IHC with calcitonin confirmed the
diagnosis.
Among the 49 patients with metastatic lung carcinomas, 45 were
adenocarcinoma, and the rest were two patients each of squamous
cell carcinoma and small cell carcinoma. Of the 45 metastatic
lung adenocarcinoma, 38 were diagnosed at the metastatic site
based on morphology and IHC with CK7, TTF1 and napsin A.
One patient with prior history of glioblastoma had multiple lytic
lesion in the rib. Biopsy revealed metastatic lung adenocarcinoma.
 Hui, et al.: Bone metastases

Table 1: Distribution and immunohistochemistry of metastatic carcinoma with known primary

Classification of metastatic tumors Number of Primary IHC markers done to Primary detected IHC markers done to detect primary
cases (%) diagnosed prior confirm primary after diagnosis
to metastasis of metastasis
Breast carcinoma 35 32(IHC‑8) Pan CK‑5/5, 3 (IHC‑3) PanCK‑2/2, GATA3‑2/2,
CK7‑1/1, GCDFP‑1/2, CK7‑1/1, ER‑1/1, CK20‑0/1, TTF1‑0/1,
Mamaglobin‑0/1, GCDFP‑0/1
ER‑4/5, PR‑3/3,
GATA3‑3/3, CK20‑0/1,
TTF1‑0/1, NapsinA‑0/1
Lung Adenocarcinoma 45 8(IHC‑3) CK7‑3/3, TTF1‑3/3, 37(IHC‑37) Pan CK ‑7/7, CK7‑28/28, TTF1‑33/33,
Napsin A‑3/3, CK20‑0/3 NapsinA ‑15/15, TG‑0/11, CK20‑0/25,
PSA‑0/5, GCDFP‑0/1, GATA3‑0/1,
ER‑0/3, CDX2‑0/3, p40‑0/1, p63‑0/1
Small cell lung carcinoma 2 2 (IHC‑2) TTF1‑2/2, Chromogranin ‑2/2,
Syanptophysin‑ 2/2, Napsin A ‑0/1,
p40‑0/1, p63‑0/1
Squamous Cell carcinoma lung 2 1(IHC) CK7‑0/1, CK20‑0/1, 1(IHC‑1) Pan CK‑1/1, CK5/6‑1/1, p63‑1/1,
p40‑1/1 TTF1‑0/1, CK20‑0/1
Adenocarcinoma Rectum 4 4 ‑ ‑
Adenocarcinoma Colon 2 1 1(IHC‑1) CK7‑0/1, CK20‑1/1, CDX2‑1/1,
TTF1‑0/1, PSA‑0/1
Renal cell carcinoma 23 7(IHC‑3) Pan CK‑3/3, 16 (IHC‑9) Pan CK‑8/8, Vimentin‑ 7/7, CD10‑8/8,
Vimentin‑3/3, CD10‑1/1, PAX8‑2/2
TTF1‑0/1, Napsin A‑0/1
Thyroid carcinoma 60 16 (IHC‑3) Calcitonin‑1/1, TTF1‑1/1, 44(IHC ‑13) CK7‑3/2, TTF1‑10/10, TG‑ 10/10,
TG‑1/1 CK19‑1/1, CK20‑0/3, PSA‑ 0/2
Prostate adenocarcinoma 12 8(IHC‑2) Pan CK 2/2, PSA ‑3/3 4(IHC‑4) PSA ‑4/4 AMCAR‑0/1, CK7‑0/1,
CK20‑0/1 CDX2‑0/1
Squamous cell carcinoma Cervix 8 8 ‑
Gastric Adenocarcinoma 2 2 ‑
Cholangiocarcinoma 1 1 ‑
Squamous cell carcinoma ‑Hypopharynx 1 1 ‑
Squamous cell carcinoma Esophagus 1 1(IHC‑1) CK7‑1/1, CK20‑0/1
Acinic cell carcinoma Salivary gland 1 1
Adenocarcinoma Gall bladder 1 1
Hepatocellular carcinoma 1 1
Adenocarcinoma arising in testicular 1 1
germ cell tumor

Table 2: Distribution of metastatic non epithelial/mesenchymal tumors

Classification of Number of Primary site Primary diagnosed IHC markers to confirm Unknown IHC markers to detect
metastatic tumors cases (%) prior to metastasis primary primary primary
Ewings sarcoma 3 Humerus‑2 3 CD99‑1/1, NSE‑0/1, TdT‑0/1 ‑ ‑
Tibia‑1
Neuroblastoma 4 Adrenal‑4 3 CD99‑2/2, NSE‑2/2, LCA‑0/1 1 CD99 1/1, NSE 1/1
Angiosarcoma 1 Lower extremity 1 CD31‑1/1, CD34‑0/1 ‑
Leiomyosarcoma 1 Kidney 1
SFT 1 Retroperitoneum 1 CD34‑1/1, CD117‑0/1, ‑
DOG1‑0/1‑
GIST 1 Ileum 1 CD117‑1/1, DOG1‑1/1 ‑
Fibrosarcoma 1 Tibia 1 ‑ ‑ ‑
Germ cell tumor 2 Testes 1 SAL4‑1/1, PLAP‑0/1 ‑ ‑
Osteosarcoma 3 Femur‑2 3 ‑ ‑ ‑
Tibia‑1
Rhabdomyosarcoma 1 Bladder 1 ‑ ‑ ‑
Paraganglioma 1 Not known/detected ‑ ‑ 1 S100‑1/1, Chromogranin
1/1, CD34 1/1, EMA 0/1
Pleomorphic Sarcoma 1 Lower Extremity 1 ‑ ‑ ‑

Of the two metastatic squamous cell carcinoma, the primary cell lung carcinoma involving the L3 L4 and C7 vertebrae. On
was detected later in one case. There were two case of small IHC, the tumor cells were positive for TTF1, chromogranin, and
720 I n d i a n J o u r n a l of Pathology and Microbiology ¦ Volume 64 ¦ Issue 4 ¦ October-December 2021
 Hui, et al.: Bone metastases

a b c d

e f g h
Figure 3: Metastatic carcinoma from primary thyroid, lung and breast.(a) Metastatic follicular carcinoma showing follicles lined by cuboidal cells
with dark staining nuclei (H and E; X100). (b) Metastatic follicular variant of papillary carcinoma showing follicles by cuboidal cells with nuclear
overlapping and clearing (H and E; X200).(c) Metastatic papillary thyroid carcinoma:(c) Papillary structures with central fibrovascular cores infiltrating
irregular bony trabeculae (H and E; X40). Inset show cells lining the papillae displaying nuclear overlapping, clearing, inclusion (black arrowhead)
and groove (black arrow) ((H and E; X400). (d‑f) Metastatic adenocarcinoma of lung: (d) Tumor cells arranged in acinar pattern (H and E; x400). (e)
Nuclear positivity of tumor cells with TTF‑1(poly HRP x 400). (f) Cells show granular cytoplasmic positivity for Napsin –A (poly HRP x 400). (g and h)
Metastatic breast carcinoma: (g) Nests of tumor cells infiltrating bony trabeculae (H and E; x 400 (h) Cells are positive for GATA 3 (poly HRP x 400)

synaptophysin. Later hilar mass was detected on CECT chest and after initial diagnosis and treatment of testicular tumor. This case
biopsy of the hilar mass confirmed the primary. has been published elsewhere.[11]

All the 35 patients with metastatic breast carcinoma were
morphologically duct cell carcinomas. All except three patients
had a prior history of breast carcinoma. Immunostaining for CK7,
CK20, GATA 3, mamaglobin, GCDFP, estrogen, and progesterone
receptors done in latter three cases to confirm the primary. The
biopsy findings of metastatic thyroid, lung, and breast carcinoma
are depicted in Figure 3.
Of the 23 renal cell carcinoma, 14 patients had conventional clear
cell carcinoma on histology. There were 16 patients who did not
have a prior history of kidney mass. Of these 16 patients, the
primary was confirmed on IHC with pancytokeratin, vimentin,
and CD10 in nine patients and the rest were diagnosed based on
morphology and imaging findings.
Apart from the eight cases of metastatic prostatic adenocarcinoma
who had a known primary, an additional four cases were
diagnosed based on morphology and IHC in correlation with
ultrasound findings and serum PSA levels. The histopathological
features of metastatic carcinoma from kidney, liver prostate and
signet ring cell carcinoma are shown in Figure 4.
There was an unusual case of metastatic adenocarcinoma
involving D9‑D12 vertebrae that developed as somatic malignancy
in a testicular immature teratoma and had metastasized 12 years
Indian Journal of Pathology and M i c r o b i o l o g y ¦ V o l u m e 6 4 ¦ I s s u e 4 ¦ O c t o b e r - D e c e m b e r 2 0 2 1 721
All except three cases of non‑epithelial tumors had known
primary prior to metastasis. The primary was detected later on
imaging in one patient of metastatic neuroblastoma and a single
case each of paraganglioma. There was a single case of metastatic
paraganglioma involving the humerus in a 45 year old female.
The tumor cells showed positivity for chromogranin and S100.
However, further details of metastatic work \‑up was not available.
The histopathological features of metastatic non‑epithelial
tumors/mesenchymal tumors are illustrated in Figures 5 and 6.
In the present study, primary site remained unknown in
146 patients. In 85 of these patients, metastatic work‑up was
either not done or details not available as many of these case were
outside referral cases. In rest, the type of work‑up was inconsistent
ranging from simple investigation to extensive work‑up. Almost
all the patients of metastatic carcinoma with unknown primary
had either metastatic adenocarcinoma or poorly differentiated
carcinoma on histology.
DISCUSSION
The skeleton is one of the most common sites for metastases,
and studies on extent of skeletal metastases have been reported
in literature.[4‑5,12,13] The recent rise detection rate of skeletal
metastasis can been attributed both to early detection becauseof
 Hui, et al.: Bone metastases

a b c

d e f
Figure 4: Metastatic carcinoma from kidney, liver prostate and signet
ring cell carcinoma.  (a‑c) Metastatic renal cell carcinoma  (clear cell
variant) (a) Nest of clear cells with small nuclei separated prominent
thin vascular channels. (H and E; X200). Tumor cells showing strong
cytoplasmic positivity with (b) Pancytokeratin (poly HRP x200) and (c)
Vimentin  (poly HRP x 200).  (d) Metastatic adenocarcinoma from
prostate showing cribriform pattern of tumor deposits within the
intertrabecular space  (H and E; x400).  (e) Hepatocellular carcinoma
displaying cords and trabeculae of polygonal cells separated by
sinusoids  (H and E; X200).  (f) Signet ring cell carcinomas showing
nests of signet cells with eccentrically placed nuclei and vacuolated
cytoplasmc (H and E; X200)
Table 3: Distribution of cases in various groups
Group Group Number Percentage
GROUP I Group IA 111 30.4
Known (Known prior to diagnosis of metastasis)
Primary Group IB 109 29.8
(Primary detected after the diagnosis of
metastasis)
GROUP II Group IIA 61 16.7
Unknown (primary remained occult even after
Primary metastatic work‑up)
Group IIB 85 23.3
(work‑up was not done or details not
available
better imaging techniques and progress in the management of
primary cancers with consequent prolonged survival.
More than two‑third of the affected patients are in the age group
of 40–60 years.[12] In the present study, 70% of patients were
between the age group of 40 and 70 years. Skeletal metastases
in children included neuroblastoma, Ewings sarcoma, and
rhabdomyosarcoma in the present study.
Pain, swelling, fracture, and neurological symptoms were the
common presenting features in our patients, which has also
been the experience of other authors.[5,14‑16] Patients with spinal
involvement mainly presented with pain and neurological
symptoms such as weakness, paresthesia and bowel, and bladder
disturbances. Pathologic fractures occur in 10–30% of patients,
most commonly affecting proximal parts of femur.[17] Pathological
fractures are encountered in 60% of breast cancer and 10% of
lung carcinoma.[18,19]
Metastases has predilection for bones with persistent red marrow
such as vertebra, proximal femur, ribs, sternum, pelvis, skull, and
722 I n d i a n J o u r n a l of Pathology and Microbiology ¦ Volume 64 ¦ Issue 4 ¦ October-December 2021
a b c
d e f
Figure 5: Metastatic non‑epithelial tumors/mesenchymal tumors.
(a and b) Metastatic neuroblastoma showing monomorphous small
round cells in fibrillary background  (H and E;  (a) X100,  (b) X200).
(c and d) Metastatic Ewings sarcoma (c) Sheets of small round cells with
scant cytoplasm and round hyperchromatic nucleus. (H and E; x400).
(d) Tumor cells are positive for CD99 (poly HRP x 400).(e) Osteoid is
laid down in between the tumor cells in metastatic osteosarcoma
(H and E x400). (f) Interlacing fascicles of spindle cells in a known case
of leiomyosarcoma (H and E; x 400)
shoulder girdle. Metastases tend to involve long bones in children
and axial skeleton in adults. More than 80% of bone metastasis
involve the axial skeleton with spine being commonest site.[16,20]
The lumbar part of the spine, is most commonly involved,
followed by thoracic, cervical, and sacral portions.[21] In the
present study, more than half of the cases involved the axial
skeleton, most frequently affecting the thoraco‑lumbar spine.
Metastases distal to elbow and knees (acral metastases) and to
facial bones are unusual.[22] The most common site distal to elbow
and knee is reported to be the tibia. In the present study, of the
total 712 metastatic skeletal sites, those distal to elbow and knee
were only 7 (tibia‑6, ulna‑1). Though scaphoid, phalanges and
semilunar bones are most commonly affected in acral metastasis,
none were involved in the present study. A high incidence of
acrometastasis is known to occur in lung carcinomas where
tumor cells embolize to all the organs, without a capillary bed
that acts as a filter.[22]
In comparison to plain radiographs which is less sensitive, CT
scans, MRI, positron emission tomography scans have better
sensitivity.[15] Plain radiographs in cases of bone metastases reveal
lytic (most common), blastic, or mixed pattern. Lung and breast
are deposits usually cause lytic destruction, but are occasionally
osteobalstic. Thyroid and kidney deposits are usually purely
lytic with prostatic deposits being osteoblastic. 599mTc bone
scintigraphy is an effective method for screening the whole body
for bone metastases especially in detecting osteolytic lesions. It
 Hui, et al.: Bone metastases
a b c
f panel of markers were used as adjunct suggests the possible origin
d e g in development of multidisciplinary treatment strategy including
Figure 6: Metastatic paraganglioma, rhabdomyosarcoma and
angiosarcoma.(a and b) Metastatic Paraganglioma: (a) Nests of polygonal
cells with clear vacuolated to pale eosinophilic cytoplasm separated
by thin vascular channels infiltrating the marrow  (H and E; x 400).
Cells are positive for (b) chromogranin (poly HRP x 400). (c) Sheets of
undifferentiated cells in a known case of rhabdomyosarcoma (H and E;
x 400). (d) Spindle cells arranged in patternless sheets with stag horn
blood vessels in a known case of solitary fibrous tumor. (H and E; x
400). (e‑g) Metastatic Angiosarcoma (g) Infiltrating tumor composed of
polygonal to spindle cells with pleomorphic hyperchromatic nucleus. (H
and E; x400). Cells are positive for (f) CD31 and (g) CD34 (poly HRP;
x 400)
also has an added advantage to screen the whole body to rule out
visceral involvement.[20]
Adenocarcinomas constitute the predominant histological type
among the metastatic bone tumors. Similar was noted in the
present study. Soft tissue and bone sarcomas metastasize to
bone with a frequency of 18%.[12] Literature suggests that breast,
prostate, lung, thyroid, and kidney account for 80–92.6% of bone
metastases.[12] In the present study, these accounted for 81.3% of
known primaries with thyroid being the most common site. Other
studies in literature reveal lung and breast to be the most frequent
sources of skeletal metastases.[12,23] This could be because of the
fact that thyroid metastases have characteristic morphology even
at metastatic site leading over representation in case with known
primaries. In contrast, the adenocarcinoma arising in other sites
do not have specific morphology. Since number of cases with
unknown primaries was high in our series, we consider that other
primary sites are underrepresented in comparison to thyroid
carcinoma among Group I patients.
Studies have shown that primary is unknown in 3–15% of all
cancer patients and 5–20% present with skeletal metastases. In
the present study, the primary remained undetected in 40% of
the patients which is higher than that reported by similar study
from India.[12] The detection rate of primaries depends upon
the diagnostic strategies used. In one series skeletal metastases
of unknown primary, a diagnostic strategy consisting of the
following: medical history, physical examination, laboratory
analysis, plain radiography involving bone and chest, whole‑body
Indian Journal of Pathology and M i c r o b i o l o g y ¦ V o l u m e 6 4 ¦ I s s u e 4 ¦ O c t o b e r - D e c e m b e r 2 0 2 1 723
techtnetium‑99‑m‑phosphonate bone scan, computed tomography
of chest, abdomen and pelvis, and finally, biopsy of the most
accessible osseous lesion, led to identification of the primary in
85% of cases.[24] However, one of the limitation of the present study
is relatively higher percent of cases with undetected primary. One
of the reasons could be reluctance on the part of oncologists to
go for extensive diagnostic work‑up in search of primary because
of lack targeted therapy in earlier years. Added to this is limited
use of IHC in metastatic work‑up and lack of organ specific/organ
restricted markers in earlier years. Immunohistochemistry with a
in cases with unknown primary in 27.4% cases in the present
study. Errani et al. in their study used IHC to establish the primary
in 52% cases in metastasis of unknown origin.[25] Recent advances
loco regional therapy and systemic use of bone targeting agents
with inhibitors of bone resorption prompts adequate diagnostic
work up for effective management.[26]
CONCLUSION
Metastases are commonest malignancy affecting skeletal sites.
More than two‑third cases of bone metastases encountered in
surgical pathology practice are as initial presentations. Spine,
femur, and pelvis are most commonly affected site. Metastatic
adenocarcinomas constitute majority of cases with thyroid,
breast, lungs, prostate, and kidney being common primary
sites. Detection rate of primary depends on extent of metastatic
work‑up. Use of IHC, especially with increasing available organ
specific/organ restricted markers increases the detection of
primary in unknown cases which in turn facilitates treatment
with targeted agents wherever available.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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