Introduction
Necrobiotic xanthogranuloma is a rare, progressive, histiocytic disease. Although it commonly involves cutaneous sites around the periorbital region, it is now considered a systemic disease which can involve the myocardium, larynx, pharynx, lungs, intestines and ovaries.Reference Finan and Winklemann1
We report the first case of necrobiotic xanthogranuloma of the parotid gland, which was diagnosed histopathologically following a subtotal parotidectomy in a 48-year-old man.
Case report
A 48-year-old Malay man presented with a four-year history of a right parotid mass which had been gradually increasing in size. There was one episode of pain, one month prior to the current presentation, which was treated by his general practitioner as acute infection. This episode was not related to meals and was not associated with any constitutional symptoms.
The patient had no known medical problems, and was found to have Type 2 diabetes mellitus only on routine blood glucose testing. Systems enquiry was unremarkable.
On examination, a firm, non-tender, mobile, 6×6 cm mass was palpable at the right angle of the mandible. There was no inflammation of Stensen's duct or any medialisation of the right lateral pharyngeal wall. Right facial nerve function was intact. The patient did not have any periorbital or subcutaneous lesions elsewhere on his body.
Fine needle aspiration cytology (FNAC) analysis of the right parotid mass revealed features consistent with Warthin's tumour.
Three months later, the patient underwent a right subtotal parotidectomy. (There had been no physical change in the mass between FNAC and surgery.)
Intra-operatively, a well-encapsulated mass was identified at the tail of the right parotid gland, extending into the deep lobe. Examination of the specimen revealed a cystic, 2.5×2.5×3 cm lesion within the right parotid gland filled with yellowish, fragile, necrotic tissue.
Microscopic examination showed sections of cystic tissue filled with necrotic material and infiltrated with chronic inflammatory cells. Numerous large foamy macrophages (Figure 1), multinucleated giant cells (Figure 2) of the Touton and foreign body-types, and cholesterol clefts (Figure 3) could be seen in a background of extensive tissue necrosis. Normal salivary gland tissue and some lymphoid aggregates were seen at the surrounding areas. There was no evidence of caseating necrosis, epithelioid granuloma or Langhans giant cells. No organisms were demonstrated on Ziehl–Neelson, periodic acid Schiff, Grocott and Giemsa staining. These features were consistent with necrobiotic xanthogranuloma. There were no histological features of the specimen suggestive of Warthin's tumour.
Photomicrograph of surgical specimen showing large, foamy macrophages (arrowheads) (H&E; ×20).
Photomicrograph of surgical specimen showing multinucleated giant cells (arrowheads) (H&E; ×20).
Photomicrograph of surgical specimen showing cholesterol clefts (arrowheads) (H&E; ×20).
Post-operatively, the patient recovered well without complication. After eight months of follow up, the patient remained well with no constitutional symptoms.
Discussion
Necrobiotic xanthogranuloma is a rare, progressive, histiocytic disease. In the World Health Organization ICD-10 classification of diseases, it falls within the category of ‘other histiocytosis syndromes’ (category D76.3). In the Medical Subject Heading classification system, it is grouped under non-Langerhans cell histiocytosis. In 1987, histiocytic disorders were classified into three categories by the Histiocyte Society Writing Group: class I (Langerhans cell histiocytosis–histiocytosis X spectrum); class II (histiocytosis of mononuclear phagocytes other than Langerhans cells); and class III (malignant histiocytic disorders).Reference Moschella2 Adult xanthogranulomatous disease falls within class II of this categorisation. It is a disease of unknown aetiology characterised by variable involvement of a spectrum of symptoms, including destructive periorbital and cutaneous lesions, multiple extracutaneous manifestations, and paraproteinaemias. The mean age of onset is the sixth decade and there is no sex predilection.Reference Mehregan and Winklemann3
In 2006, Sivak-Callcott et al. organised a multi-institutional effort to study adult xanthogranulomata, and were able to categorise it into four syndromes based on histopathological, immunohistochemical, clinical and systemic features, as follows: (1) adult onset xanthogranuloma (solitary lesion without systemic findings); (2) adult onset asthma and periocular xanthogranuloma; (3) necrobiotic xanthogranuloma; and (4) Erdheim–Chester disease.Reference Sivak-Callcott, Rootman, Rasmussen, Nugent, White and Paridaens4
Necrobiotic xanthogranuloma is characterised by the presence of multiple, indurate, yellow-red plaques in the head and neck area (especially the periorbital region) and trunk; however, although characteristic, such lesions are not necessary for diagnosis.Reference Chave and Hutchinson5
Eighty per cent of necrobiotic xanthogranuloma cases have been associated with paraproteinaemia; the most common type is immunoglobulin (Ig) Gκ monoclonal gammopathy (60 per cent), followed by IgGλ (26 per cent) and IgA.Reference Finan and Winklemann1, Reference Martinez Fernandez, Rodriguez Prieto, Ruiz Gonzalez, Sanchez Sambucety and Delgado Vicente6 In 10 per cent of cases, the monoclonal gammopathy develops into multiple myeloma.Reference Martinez Fernandez, Rodriguez Prieto, Ruiz Gonzalez, Sanchez Sambucety and Delgado Vicente6
A review of necrobiotic xanthogranuloma by Finan and Winklemann revealed the involvement of extracutaneous sites such as the spleen, lung, kidney, intestine, ovary, skeletal muscle and central nervous system.Reference Finan and Winklemann1 The larynx and pharynx are the only sites within the head and neck region reported to be involved with necrobiotic xanthogranuloma.
Necrobiotic xanthogranuloma can be histologically characterised by: xanthomatised histiocytes; giant, bizarre foreign body cells; Touton cells; lymphocyte aggregates; cholesterol clefts; and areas of severe necrobiosis.Reference Finan and Winkelmann7
Because of the rarity of this disease, the outcome of therapy is difficult to evaluate, as multiple therapeutic modalities have been used in all the syndromes, including chemotherapy, interferon (α-2b or α-2a), plasmapheresis, intralesional steroid injections, cryotherapy, radiation therapy and surgery.Reference Finan and Winkelmann7–Reference Elner, Mintz, Demirci and Hassan13 The best results have been obtained with multiagent chemotherapy, with or without radiation or surgery.Reference Sivak-Callcott, Rootman, Rasmussen, Nugent, White and Paridaens4 Sivak-Callcott et al. also recommend characterisation of histiocytes and correlation with histopathological B and T cell findings, when choosing an immunosuppressive agent for treatment.Reference Sivak-Callcott, Rootman, Rasmussen, Nugent, White and Paridaens4
To our knowledge, the current patient represents the first reported case of necrobiotic xanthogranuloma of the parotid gland. This is a different histological entity to xanthogranulomatous sialadenitis, a handful of cases of which have been reported.Reference Cocco, MacLennan, Lavertu and Wasman14
• Necrobiotic xanthogranuloma is a rare, progressive, histiocytic disease
• It is a systemic disease which may involve cutaneous and extracutaneous sites, and which is associated with paraproteinaemias
• Necrobiotic xanthogranuloma may present as a swelling of the parotid gland
• For an isolated swelling, surgical excision is a reasonable management option
In our patient, the diagnosis was made from the classical histological features of necrobiotic xanthogranuloma. Because the lesion was removed in its entirety during the subtotal parotidectomy, and the patient did not show any manifestation of cutaneous or systemic necrobiotic xanthogranuloma, the decision was made to follow him up expectantly.
