C A S E R E P O R T
Castleman’s disease presenting within the cheek of a child
S. Katti1*, M.A. Bussell2*, P. Najran3, A. ElRasheed4, R.J. Prescott5& J.G. Smith6
1Department of Histopathology, Royal Lancaster Infirmary, Lancaster, UK
2Oldham Primary Care Trust, Cannon Street Health Centre, Oldham, UK
3Department of Oral and Maxillofacial Surgery, Royal Blackburn Hospital, Blackburn, UK
4Department of Oral and Maxillofacial Surgery, Royal Blackburn Hospital, Blackburn, UK
5Department of Histopathology, Royal Blackburn Hospital, Blackburn, UK
6Department of Oral and Maxillofacial Surgery, Royal Blackburn Hospital, Blackburn, UK
Abstract
A case is presented of an 11-year-old male with an eventual diagnosis of extranodal Castleman’s disease (hyaline vascular type). This was difficult to diagnose as attempts were made to remove what was believed to be a hae- matoma, and then a reactive lymph node within the left cheek. Subsequent histopathology revealed the true nature of this swelling.
Key words:
cheek, child, extranodal Castleman’s disease, history of trauma
Correspondence to:
MA Bussell
Birmingham Dental Hospital St. Chad’s Queensway Birmingham B4 6NN UK
Tel.: 0121 236 2818 Fax: 0121 237 2750
email: maryalicebussell@hotmail.com Accepted: 19 August 2008
doi:10.1111/j.1752-248X.2008.00036.x
Introduction
Castleman’s disease was first described in 1954 (by Castleman and Towne)1. Further development has suggested that Castleman’s disease is a lymphopro- liferative disorder. The disease can present in lymph nodes or as an extranodal mass. The disease has also been termed angiofollicular lymph node hyperplasia, giant lymph node hyperplasia and angiomatous lymphoid hamartoma2. The aetiology of the disease remains unknown, but proposed theories include a response to chronic infection3,4, hypersecretion of the cytokine IL-65and a hamartoma of lymphoid tissue6.
Clinically, the lesion typically presents as a solitary mass, which is benign, painless and without specific signs or symptoms. It can also present as multicentric masses7. The disease tends to be seen in young adults and there is no sexual predilection.
The most common site of presentation is in the mediastinum (in 86% of cases), followed by the neck (in 6% of cases)3. Less commonly, cases have been reported in the head and neck region, including the parotid gland8, submandibular gland9 and within a lymph node in the buccal mucosa10.
Histopathologically, two main variants of Castle- man’s disease have been identified; the first, hyaline vascular type (80–90%)3,11, is characterised histologi- cally by lymphoid follicular hyperplasia with abnormal, regressive germinal centres. Dysplastic follicular den- dritic cells are surrounded by concentrically layered mantle cells. There is intrafollicular capillary prolifera- tion and hyalinisation3. This variant is usually asymp- tomatic, unless the lesion causes indirect symptoms by compression of adjacent structures12.
The second variant is the plasma cell type (10–
20%)3, which shows an increase in the number of plasma cells in the interfollicular region3. This variant often has associated systemic symptoms, such as fever,
*The first two authors contributed equally to this paper.
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night sweats, anaemia and hypergammaglobuline- mia13. This form of the disease is more aggressive and has a relatively poor prognosis. It has been associated with the human herpes virus 8 (HHV8) infection, in which patients have an increased risk of developing other HHV8-associated neoplasms, for example, Kapo- si’s sarcoma and B-cell plasmablastic lymphoma14.
Intermediate variants of the hyaline vascular and plasma cell types have been also described15.
Case presentation
An 8-year-old Caucasian male presented with a 2-week history of swelling within the substance of the left cheek. The lump was first noticed following an injury to the left cheek while playing rugby. Failure of the lesion to reduce in size resulted in a referral to oral and maxillofacial surgery by his general medical practitioner.
Upon examination, the patient was systemically well with no cervical lymphadenopathy. A 1.5 cm diameter, non-tender, fluctuant, smooth mass was found within the left cheek, overlying the zygomatic bone. A full blood count and erythrocyte sedimentation rate were within normal limits and facial radiographs were unremarkable. The provisional diagnosis of an organ- ising haematoma was made. The patient was then reviewed over a 4-month period, during which time there was no significant change.
As the lesion had not resolved, an exploration of the left cheek and excisional biopsy was performed under general anaesthetic. The lesion was approached from an intraoral incision; following blunt dissection, the mass was found within subcutaneous tissue and muscle, deep within the left cheek, just below the malar prominence. The lesion was solid in nature and there was no definitive plane between the lesion and surrounding tissue. Histopathological analysis revealed reactive lymphoid hyperplasia with no malignancy.
After 7 months, the lesion reoccurred in the same location and further removal was performed under general anaesthetic. Histopathological examination of this sample was reported as showing soft tissue with a reactive lymphoid infiltrate composed of reactive lymphoid follicles with regressive germinal centres.
The latter showed vascular proliferation and focal hyalinisation. The mantle zone appeared expanded and showed the classical ‘onion skin’ concentric layer- ing of lymphocytes at the periphery of the follicles (see Figs. 1 & 2). No lymph node capsule or sinuses were evident.
A diagnosis of extranodal, soft tissue, hyaline vascu- lar type Castleman’s disease was made. The lesion was
felt to be completely excised and the patient now remains symptom-free, although continuing under regular review.
Discussion
Castleman’s disease is a rare lymphoproliferative disorder, which has the potential to progress to malignancy.
Most frequently, it presents in the mediastinum of young adults3. Although rare, the disease has been reported in children16.
This reported case is believed to be a unique example of extranodal, hyaline vascular Castleman’s disease,
Figure 1 Regressed germinal centres surrounded by concentric layering of mantle zone lymphocytes. The interfollicular stroma is prominent with numerous post-capillary type blood vessels.
Figure 2 Germinal centre showing dysplastic dendritic cells and promi- nent hyalinised blood vessels.
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217 Oral Surgery1 (2008) 216–219. © 2008 John Wiley & Sons A/S
which presented intraorally, within the substance of the cheek of a child, following a history of trauma.
Diagnosis of the disease is a challenge to the clinician and can be readily misdiagnosed2. The aforementioned case highlights this difficulty, as initially, the lesion was diagnosed clinically as a haematoma. The first histo- pathological investigation reported the lesion as reac- tive lymphoid hyperplasia. Only after the recurrence and second excision was a histopathological diagnosis of Castleman’s disease made.
A haematoma is not routinely included in the dif- ferential diagnosis of Castleman’s disease. However, because of marked ‘vascular infiltration’, and therefore the vascular nature of this lesion, it may clinically mimic a haematoma.
It is postulated that increased IL-6 production by the mantle zone B-lymphocytes secondary to stimulation by HHV-8 or by an unidentified exogenous or endog- enous agent, is the initial step in the development of Castleman’s disease17. IL-6, in turn, stimulates release of vascular endothelial growth factor, resulting in the characteristic lymphoid follicular and vascular prolif- eration18. The aforementioned case manifested subse- quent to a traumatic event. It remains to be seen if trauma can induce localised IL-6 production and sub- sequent Castleman’s disease-like changes, or whether trauma can cause an already existing vascular Castle- man’s lesion to bleed and form what mimics an organ- ised haematoma.
Following complete surgical excision, clinical reso- lution of the disease usually occurs11. In this case, the recurrence is most likely to have arisen within the residual tissue, suggesting an incomplete initial exci- sion. Ten months following the second procedure, the patient has remained symptom-free.
In summary, this distinctive case reports a localised, extranodal, soft tissue, hyaline vascular Castleman’s disease, occurring in the cheek of a child following trauma. It is an unusual example of an extremely rare pathological condition to occur intraorally and within the paediatric population. It has presented a diagnostic challenge to both clinician and pathologist.
Acknowledgement
The authors thank S Banerjee, Consultant Histopatho- logist, for his assistance in the diagnosis of this case.
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