Denosumab for central giant cell granuloma in an Australian tertiary paediatric centre.

BACKGROUND: Central giant cell granulomas (CGCG) are rare osteolytic, benign but often locally aggressive tumours of bone. Surgical curettage may not be possible in extensive lesions and resection carries high morbidity, especially in growing children, and previous medical therapies have had variable efficacy and high recurrence rates. Interruption of receptor activator of nuclear factor-kappa B ligand (RANKL) signalling holds promise as an effective therapeutic strategy for these tumours. AIMS: To evaluate the efficacy and safety of our protocol for denosumab treatment of CGCG in children. METHODS: Retrospective review of 4 patients treated with denosumab using a standardised protocol for CGCG in a tertiary paediatric centre. Denosumab 70 mg/m2 was given 4-weekly, followed by 2 doses of zoledronate 0.025 mg/kg, aimed at preventing rebound hypercalcaemia. RESULTS: Treatment of CGCG resulted in metabolic remission in all patients, but recurrence, detected by positron emission tomography (PET), occurred at 6 months in three patients and 12 months in one patient. Three patients developed symptomatic hypercalcaemia 4-5 months and one patient asymptomatic hypercalcaemia 7 months after cessation of denosumab, with 3 requiring additional bisphosphonate treatment. CONCLUSIONS: Denosumab produced a radiological and metabolic response in our patients, but metabolic recurrence occurred in all patients. PET imaging was effective for monitoring treatment response and early detection of recurrence. Incidence of rebound hypercalcaemia in this paediatric cohort was high. We present proposed changes to our protocol with the aim of producing sustained remission and preventing rebound hypercalcaemia.

Periocular mass lesions secondary to dermatologic fillers: report of 3 cases.

OBJECTIVE: To describe findings in patients who received dermal fillers and later developed peri-ocular mass lesions. DESIGN: Retrospective case series. PARTICIPANTS: Patients who presented with peri-ocular masses secondary to dermal filler use. METHODS: Retrospective chart review. RESULTS: Three patients with remote filler injection (hyaluronic acid and polyalkylimide), not volunteered on initial history, presented with peri-orbital swelling and/or inflammation that was suspicious in each case for more serious pathology. CONCLUSIONS: It is important for the injecting physician, the ophthalmologist, and the patient to recognize this complication to permit appropriate investigation and management.

Unusual presentation of altered bone metabolism with long-term antiepileptic therapy: pathological fracture of neck of femur due to brown tumor at calcer.

The antiepileptic drugs are known to alter the bone metabolism and result in various range of pathological conditions (osteoporosis, osteomalacia, vitamin D deficiency, secondary hyperparathyroidism). These clinical conditions developed either due to direct effect of these therapeutic agents on bone or due to alteration in the homeostasis of other regulators of bone metabolism like serum calcium, vitamin D, and parathyroid hormone. Long-term therapy with antiepileptic agents results in higher incidence of pathological fracture, which is a consequence of either osteoporotic or osteomalasic (secondary to vitamin D deficiency) changes in bone produced by these drugs. Secondary hyperparathyroidism due to vitamin D deficiency following long-term polytherapy of antiepileptic drug ultimately leading to development of brown tumor and pathological fracture is very unusual.

Orofacial granulomas after injection of cosmetic fillers. Histopathologic and clinical study of 11 cases.

BACKGROUND: Purposely, cosmetic injections in orofacial tissues of various resorbable, biodegradable, or permanent fillers may be followed by development of foreign-body granulomas. The aim of this article is to contribute to the histologic identification of the filler material. METHODS: Histologic and clinical features of 11 cases of granulomas on orofacial fillers are described. RESULTS: Only 3/11 patients knew the nature of the injected product. Four histologic patterns were found: (i) Artecoll, (ii) Dermalive, and (iii) New-Fill granuloma, all three of the classic giant cell granuloma type, differing in respect of foreign particles; and (iv) Liquid Silicone granuloma, which featured a cystic and macrophagic type. Information was often missing or misleading, patients or practitioners being reluctant to give the details. CONCLUSION: Increasing demand for orofacial tissue augmentation makes pathologists face new, and sometimes, puzzling granuloma types. Identification of the foreign product might be required for therapeutic or medico-legal reasons.

[Sarcoidal allergic contact dermatitis due to palladium following ear piercing]. / Sarkoidale allergische Kontaktdermatitis auf Palladium nach Ohrpiercing.

Granulomatous tissue reactions due to jewelry made of gold, silver, nickel and palladium are rare but nevertheless have been known for a long time. A female patient developed nodular infiltrates after having been pierced with ear stickers containing palladium. A contact allergic reaction could be demonstrated as the underlying cause by inducing similar histological changes following patch testing with palladium.

Myospherulosis complicating cortical block grafting: a case report.

BACKGROUND: Myospherulosis of the oral cavity is an inflammatory, granulomatous lesion historically associated with the use of petrolatum-based antibiotic ointment placed in third molar extraction sites to prevent postoperative infection. METHODS: A case of bilateral myospherulosis is presented, in which large lesions complicated the procurement of a cortical block graft used to prepare a mandibular molar edentulous space for implant placement. By obtaining the block graft from a more lateral location on the mandible, an adequate graft was procured and was successfully grafted into an atrophic edentulous ridge. RESULTS: The cortical block graft was successfully incorporated by the recipient site, which received a wide-body, threaded dental implant 6 months later. Healing was uncomplicated, and a functional implant-supported restoration was successfully achieved. CONCLUSIONS: Myospherulosis, though rare today, may present a significant obstacle to the procurement of cortical block grafts. In this case, thorough debridement of the material resulted in subsequent healing of the myospherulosis defect, but prevented procurement of the cortical graft from the planned site. The dimension and volume of the neighboring cortical bone were adequate, and the augmented edentulous space was subsequently restored with a functional endosseous implant. The success seen in these 2 sites would seem to confirm the assumption that size and location of myospherulosis defects are critical factors in obtaining a successful clinical result in implant patients.

Giant cell myocarditis as a manifestation of drug hypersensitivity.

Adverse drug effects on the myocardium are often classified into toxic and hypersensitivity forms of myocarditis, each with distinct histologic findings. In contrast, giant cell myocarditis (GCM) is generally not associated with adverse drug reactions and has unique histopathologic features. We report four cases of adverse drug reactions in which the histologic findings were characteristic of GCM. The clinical recognition that GCM may be a manifestation of an adverse drug reaction is important, since the prognosis and treatment of this entity may be different from that of other forms of myocarditis.

Adverse effects of bone wax in surgery of the orbit.

The goal of this article is to establish the incidence and scope of adverse reactions to bone wax in a large orbital surgical series. We report two patients with bone wax granulomas of the orbit as a remote surgical complication. These are the first reported cases of adverse reactions to bone wax in the ophthalmic literature. A chart review was conducted on all patients from the University of British Columbia Orbit Clinic that had surgery with temporary or permanent removal of orbital bone. Two patients with bone wax granulomas were identified. In one case, intraoperative cultures grew Staphylococcus aureus, confirming that the wax may indeed act as a nidus for infection. No cases of pseudoarthrosis have occurred. This syndrome of chronic granulomatous giant cell foreign body inflammation has characteristic clinical, radiologic, and histopathologic features. The literature regarding adverse reactions to bone wax is reviewed, and specific implications for orbital surgery are discussed.

Fluoxetin-induced pulmonary granulomatosis.

A patient treated with fluoxetin for a manic depressive disorder developed pulmonary inflammatory nodules with noncaseating giant cell granulomas, interstitial pneumonia and non-necrotizing vasculitis, whilst remaining asymptomatic. A progressive resolution of pulmonary nodules occurred after withdrawal of the offending agent, and the chest radiograph returned to normal in 9 months. The diagnosis was assessed by an open lung biopsy.

[Sclerosing lipogranulomatosis of the eyelids after ethmoid sinus surgery: a complication after ointment tamponade!]. / Sklerosierende Lipogranulomatose der Augenlider nach Siebbeinoperation: eine Komplikation nach Salbentamponade!

We report on an instructive case of an infrequent but severe complication after paranasal sinus surgery. The use of ointment-covered nasal packing for haemostasis can cause inoculation of ointment into the orbita, if the medical orbital wall has been injured intraoperatively. A postoperative intraorbital haematoma may spread ointment droplets into subcutaneous tissues of the eyelid and cause local sclerosing lipogranulomatosis. The case reported here underlines the resulting therapeutical problems as have been mentioned in the literature. Only complete excision of the lipogranuloma can prevent recurrences. We conclude that ointment should not be used with nasal packings after paranasal sinus surgery if an intraoperative lesion of the orbital wall is likely to occur.

Granulomatous tissue reaction and calcification of heterologous elastin implanted in hairless mouse skin: light and electron microscopic studies compared with reaction of heterologous collagen.

Heterologous elastin particles were injected into the deep dermis or below the panniculus carnosus of hairless mice. A granulomatous tissue reaction with concomitant giant cell formation occurred around the implanted elastin in the early stages and, subsequently, calcium deposition with disappearance of the histiocytes and giant cells occurred in the later stages. Ultrastructural study revealed that some elastin particles were engulfed by the giant cells; others underwent calcification but remained intact. The heterologous collagen used as a control also induced a granulomatous tissue reaction, but did not undergo calcification and gradually disappeared. These results suggest that the heterologous elastin and collagen particles exhibit different susceptibilities to digestion. However, it is not clear why the heterologous elastin underwent calcification.

Therapy-resistant foreign body giant cell granuloma at the periapex of a root-filled human tooth.

Although the primary etiological factor of periapical lesions is microbial, there are other independent factors that can adversely affect the outcome of endodontic treatment. In this communication, we present morphological evidence in support of the role of a foreign body reaction of periapical tissue to root-filling materials. The specimen consisted of a surgical biopsy of an asymptomatic periapical lesion which persisted after a decade of postendodontic follow-up. The biopsy was processed for correlated light and electron microscopy and was analyzed by various microtechniques. The unique feature of the lesion was the presence of vast numbers of large multinucleated cells and their cytoplasmic inclusion bodies. Morphologically, these multinucleated cells resembled foreign body giant cells. They contained characteristic birefringent cytoplasmic inclusions which on electron-probe X-ray microanalysis consistently revealed the presence of magnesium and silicon. The magnesium and silicon are presumably the remnants of a root-filling excess which protruded into the periapex and had been resorbed during the follow-up period. These observations strongly suggest that in the absence of microbial factors, root-filling materials which contain irritating substances can evoke a foreign body reaction at the periapex, leading to the development of asymptomatic periapical lesions that may remain refractory to endodontic therapy for long periods of time.