JIGSAW PUZZLE -A CLASSICAL DOSSIER OF PAGET'S DISEASE

Abstract

Paget's disease (PD) is a chronic bone disease characterised by increased resorption followed by excessive bone formation resulting in bone pain and fractures. PD is most common in the elderly and many are initially asymptomatic but can develop severe complications as disease progresses. Serum alkaline phosphatase is an important biochemical marker which is elevated in these patients. A clinical lion like face and radiological "cotton wool appearance" and a "jigsaw puzzle" pattern on histopathological examination are the characteristic features of PD. Bisphosphonates are the most commonly used drug of choice for treatment of patients with Paget's disease. We discuss a classic case of PD involving a 70 year old female in this case report.

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International Journal of Head and Neck pathology
Case Report
JIGSAW PUZZLE - A CLASSICAL DOSSIER OF
PAGET’S DISEASE
Sandra Sagar 1, Karthikeyan Ramalingam 2*, Pratibha Ramani 3
1Department of Oral & Maxillofacial Pathology, Saveetha Dental College & Hospitals, Chennai – 6000077
2* Professor and Head, Department of Oral & Maxillofacial Pathology, Saveetha Dental College & Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai – 6000077
3 Professor & Head, Department of Oral & Maxillofacial Pathology, Saveetha Dental College & Hospitals, Chennai – 6000077
How to cite: Sagar S et al, Jigsaw Puzzle - A Classical Dossier of Paget’s Disease. Int J Head Neck Pathol 2022;
5(2):1-6. DOI: https://doi.org/10.56501/intjheadneckpathol.v5i2.554
Received :24/06/2022 Accepted: 15/07/2022 Web Published: 29/07/2022
Abstract
Paget’s disease (PD) is a chronic bone disease characterised by increased resorption followed by excessive
bone formation resulting in bone pain and fractures. PD is most common in the elderly and many are initially
asymptomatic but can develop severe complications as disease progresses. Serum alkaline phosphatase is an
important biochemical marker which is elevated in these patients. A clinical lion like face and radiological
“cotton wool appearance” and a “jigsaw puzzle” pattern on histopathological examination are the
characteristic features of PD. Bisphosphonates are the most commonly used drug of choice for treatment of
patients with Paget’s disease. We discuss a classic case of PD involving a 70 year old female in this case
report.
Keywords: Paget’s disease, Lion-like face, Cotton wool, Jigsaw puzzle
Address for Correspondence:
Dr. Karthikeyan Ramalingam,
Associate Dean, Professor and Head,
Department of Oral Pathology,
Saveetha Dental College and Hospitals,
Saveetha Institute of Medical and Technical Sciences,
Chennai, Tamilnadu, India.
Email: karthikeyanr.sdc@saveetha.com
© 2022 Published by MM Publishers.

2 Sagar S et al. Jigsaw Puzzle – Paget’s Disease – A Dossier.
INTRODUCTION
Paget disease of bone (PD) is characterized by abnormal deposition and resorption of bone leading to
weakening of bones. Sir James Paget, a British surgeon was the first to describe Paget’s disease in 1877. It is
most commonly seen among the elderly people. PD can be either monostotic or polyostotic. The exact
cause of Pagets disease is still unknown, however recent studies have shown that mutation in the sequestrome
gene (SQSTM1) gene which plays a role in the osteoclastic activity bia nuclear factor-κB have a potent role in
the etiology of PD. [1] PD is characterized by active bone remodeling, which leads to pain and pathological
fractures.
CASE REPORT
A 70 year old female patient reported to the clinic with the chief complaint of right upper and lower back
tooth for past 3 years which aggravates on mastication and relieves on taking medications. Patient had no
relevant medical and surgical history. Patient had difficulty in hearing for the past 3 years. On extra-oral
examination, there was evidence of bilateral swelling seen over the zygomatic region, obliterating the
nasolabial sulcus. The patient had the characteristic leonine facies. On palpation, the swelling was hard in
consistency. The swelling was immobile and attached to the underlying bone. Intra-orally, there was a
swelling seen in the 18 region of the maxillary alveolus [Fig.1] with obliteration of the buccal sulcus. Cortical
expansion was seen in the maxillary molar region. On palpation, the swelling was non-tender, consistency
was hard and attached to the underlying bone. [Fig.2]
Figure.1 Extraoral clinical photographs showing diffuse swelling of the face giving a leonine facies
appearance.

Sagar S et al / Int J Head Neck Pathol.2022; 5(2):1-6. 3
Figure.2 Intraoral clinical photographs showing cortical expansion in relation to right maxillary molar
region
On radiographic examination, mixed radiopacities were evident in the skull vault, facial bones and sinus
involvement, suggestive of cotton wool appearance [Fig.3]
Figure.3 Radiograph of the skull shows irregularly shaped radiopacities involving the entire skull,
giving a characteristic cotton wool appearance.
An incisional biopsy was done in relation to 18 region and was submitted for histopathological examination.
On grossing, a single bit of hard tissue specimen was received in formalin, hard in consistency, measuring
0.5x0.3x0.2 cm, black in colour. The tissue bit was kept for decalcification in 10% formic acid followed by
routine tissue processing.[Fig.4]

4 Sagar S et al. Jigsaw Puzzle – Paget’s Disease – A Dossier.
Figure 4: Grossing image showing the tissue specimen
Histopathological examination showed irregular bony trabeculae with prominent basophilic reversal lines,
numerous osteocytes within the lacunae and simultaneous areas of bone formation and bone resorption. The
areas of bone formation showed the presence of bony trabeculae lined by plump osteoblasts. The areas of
bone resorption are seen surrounded by multi-nucleated giant cells. The intervening connective tissue stroma
was fibrovascular with mild chronic lymphoplamacytic infiltrate. Areas of haemorrhage were also
seen.[Fig.5]
Figure 5 Photomicrographs showing jig-saw puzzle pattern of bony trabeculae with osteocytes along
with prominent basophilic reversal lines and multinucleated giant cells. ( H & E, 10x/40x)
Correlating the clinical, radiologic, and histopathologic findings, a final diagnosis of Paget’s disease of bone
was established. Patient was referred for further evaluation of alkaline phosphatase levels and was advised a
bone scan for further evaluation .
DISCUSSION
PD is the second most common bone disorder with osteoporosis being the most common. PD was found to be
more common among the western countries, however it has been increasingly reported in Asian countries in
the recent times.[1]
PD commonly affects elderly people over the age of 40 and it most often presents as an incidental finding
during radiographic examination. Fractures, either pathologic or traumatic are more common in later stages of
the disease progression. Radiological and histopathological examination usually provide the diagnosis of PD.
The exact cause of PD is still unclear. However genetic factors play a great role in this disease since most of
the affected patients have a positive family history of the disease. The initial finding of PD is often incidental

Sagar S et al / Int J Head Neck Pathol.2022; 5(2):1-6. 5
with an elevated serum alkaline phosphatase level or an incidental finding during radiograph examination.
Though the patients appear to be asymptomatic initially, they develop bone pain and fractures due to the
expansion of bone and compression of adjacent neural structures. The overlying skin in those regions of bone
expansion may be warm due to the increased vascularity associated with high bone turnover.[2,3]
Maxilla is the most commonly affected site followed by mandible. Cortical expansion of the maxillary
alveolus and flattening of the palate is the most commonly observed feature.In edentulous patients, there is a
common complaint of ill-fitting dentures. Leontiasis Ossea or lion like facies, characterised by enlargement of
mid third of the face is seen in PD, but it may also be seen in patients who have advanced lepromatous
leprosy. [1-3] In this present case also, the patient had a lion like appearance of the face.
PD is diagnosed primarily by radiological examination. During the early course of the disease, there is a
predominant lytic activity followed by sclerosis giving the characteristic cotton wool appearance, thickened
trabeculae, bone expansion, cortical thickening, and deformity.[4] Our case presented with classical cotton
wool appearance involving the craniofacial bones. A differential diagnoses of lytic or sclerotic metastasis
should also be considered for localised lesions, though the radiological appearances are usually
characteristic.[5] The other classic radiographic appearances seen in various bones affected by PD are “blade
of grass”, “flame sign” , “Brim sign” and, “TamO’Shanter” skull are, which were not seen in our case. [6]
Histopathological examination shows an alternating resorption and formation of bone. In the active
resorptive stages, numerous osteoclasts are seen surrounding the bony trabeculae and the osteoblastic
activity is seen with formation of osteoid rims around bony trabeculae. A highly vascular fibrocellular
connective tissue replaces the marrow. A characteristic microscopic feature is the presence of
basophilic reversal lines in the bone. These lines indicate the junction between alternating resorption
and formation that results in a “jigsaw puzzle,” or “mosaic,” appearance of the bone. [1,2] Our case
showed the classical jigsaw puzzle apperance.
Patients with PD show an elevated serum alkaline phosphatase levels but blood calcium and phosphorus
levels are usually normal. Hence the patients must be advised to evaluate the serum alkaline phosphatase
levels. The clinical and radiographic features, are sufficient for initial diagnosis, histopathological
findings and biochemical examination provides the confirmatory diagnosis. In most of the cases, patients are
assymptomatic and require no treatment. However NSAIDs and bisphosphonates are the most commonly used
treatment for patients with the advanced forms of Paget’s disease.[1,2,7]
CONCLUSION
Though patients with PD are asymptomatic initially, an early diagnosis and prompt treatment can save the
patient from the complications associated with the disease progression.
Financial support and sponsorship
Nil
Conflicts of interest
There are no conflicts of interest

6 Sagar S et al. Jigsaw Puzzle – Paget’s Disease – A Dossier.
Copyright ©2022 Sandra Sagar, Karthikeyan Ramalingam, Pratibha Ramani
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