PÁGINA DEL RESIDENTE

What should the diagnosis and treatment be?

¿Cuál sería su diagnóstico y su manejo terapéutico?

A 44 year-old woman was seen for severe jaw stiffness of 4 months’ duration after a lower left third molar extraction followed by odontogenic infection at another center. She could only open her mouth 8 mm. No active infective processes were detected in the physical examination; palpation of the masseter and medial pterygoid muscles elicited intense pain. Conventional blood tests did not reveal any abnormality. Based on a presumptive diagnosis of trismus secondary to odontogenic infection, nonsteroid anti-inflammatory agents and muscle relaxants were prescribed. Three months after the initial diagnosis, the patient showed no improvement. Cervicofacial computed tomography (CT) did not disclose any alteration. The patient was diagnosed of fibrous ankylosis and underwent surgery with general anesthesia and nasotracheal intubation to force her oral cavity open and insert a rubber bite opener to maintain the opening between the right dental arches in the premolar and molar region. The patient continued with the bite opener for 4 months. The appliance was removed and replaced in successive follow- up examinations of the oral opening achieved. The stable interincisor distance achieved after this treatment was 35 mm.

One month later, the patient was seen for a soft, painless mass of the right mouth floor, adjacent to the mandibular lingual cortical, that extended from the canine to the molar region. The lesion was excised completely with the sublingual gland. The histological diagnosis was interstitial lymphocytic infiltration of a salivary gland and periglandular acute and chronic inflammation. The epithelium exhibited normal stratification without atypia, with proliferation of vascular structures with prominent endothelium in the superficial connective tissue lymphocyte infiltrate, eosinophilic granulocytes, and reactive fibroblastic cells. A focal histiocytic reaction with foreign-body giant multinucleate cells and fibrinoid material was present. The initial pathology diagnosis was angiolymphoid hyperplasia with eosinophilia. In a new intervention, the lesion was resected under general anesthesia. Despite the absence of incidents or local recurrence in the postoperative period, two months after surgery the patient was seen again for three subcutaneous soft masses in the right submandibular region with diameters ranging from 10 to 15 mm (Fig. 1). The posterior nodule had fistulized to skin and secreted purulent material. Cytology of the fine needle aspiration biopsy material revealed nonspecific abscess-like material.

Submandibular foreign-body granuloma. Migration of aluminum silicate particles from the oral mucosa

Granuloma de cuerpo extraño en región submandibular. La migración de partículas de silicato de aluminio desde la mucosa oral

R. González-García¹, F.J. Rodríguez Campo², J. Sastre Pérez², V. Escorial Hernández², P.L. Martos¹, M. Mancha de la Plata¹, M.F. Muñoz-Guerra², L. Naval-Gías²

1 Médico Residente.
2 Médico Adjunto.
Servicio de Cirugía Oral y Maxilofacial.
Hospital Universitario La Princesa. Madrid, España

Correspondence

Biopsy of the nodules demonstrated a lympho-histiocytic reaction with foreign body giant multinucleate cells. Darkblack birefringent particles were visible (Fig. 2). Most of the lymphocytes exhibited a positive CD8 immunophenotype. Some cells showed CD4 positivity with an increased cellular growth fraction (Ki-67). Gradual formation of small subcutaneous and intradermal nodules containing dark blue pigment and numerous small pustules was observed. The histological diagnosis was foreign-body granuloma. The patient denied any local application of cosmetic products or injection of soft tissue fillers. Medical treatment consisting of doxycycline and cortisone, in doses of 60 mg/day the first month, 30 mg/day during the following month and a half, and 15 mg/day the last 15 days, was prescribed. The small nodular intradermal and subcutaneous formations were removed by local surgical debridement. The diagnosis of foreign body reaction was confirmed by histology. The lesion did not recur in the 6 months after treatment.

Several samples of the material resected in the submandibular region and the trismus appliance were sent to the National Institute of Toxicology and Forensic Science for analysis of the inclusions. Various study techniques were used: optical microscopy, infrared micro-spectrophotometry with Fourier’s transformation (FT-IR), and scanning electron microscopy with energy-dispersive X-rays (SED-EDX). Analysis of the fragments from the trismus appliance revealed a silicone spectrum by FT-IR and silica by SEM-EDX. Aluminum, iron, and nickel from the metal washer of the trismus appliance were identified by SEM-EDX. The PK sample of resected tissue was treated with proteinase K (Fig. 3). Spectra of glycoproteic material and silica were obtained by FT-IR and silica, sulfur, and aluminum were the majority components obtained by SEM-EDX. Other elements, such as calcium, potassium, iron, sodium, chromium, and titanium, were isolated in smaller concentrations. The PKN sample of resected tissue was treated with proteinase K and nitric acid (Fig. 4). Spectra of aluminum silicate were observed by FT-IR. Silica and aluminum were isolated as the predominant elements by SEM-EDX. Other elements, such as iron, calcium, potassium and sodium, were identified in moderate concentrations, whereas titanium, magnesium, sodium and barium were detected in very small concentrations. The results indicated that aluminum silicate was present in the tissues examined.

Discussion

Particle migration is a phenomenon rarely reported in relation to treatment with injectable soft tissue fillers like silicone, polyacrylamide hydrogel, poly-L-lactic acid, Artecoll^®, hyaluronic acid, Dermalive^®, Gore-Tex^®, and others. Injected microsphere migration has been studied experimentally. According to Lemper et al.,¹ polymethylmetacrylate microspheres seem to be the most stable particles, whereas polylactic acid induces foreign body reactions that are characterized by the recruitment of macrophages, giant cells, and elastic fibers. Characteristically, when macrophages have phagocytized a large number of these particles (> 10) as giant cells, they cannot move and migrate. We believe that this mechanism may explain the appearance of several foci of foreign body granulomatous reaction along a specific line of migration, as observed in the present case. Three mechanisms are implicated in particle migration at a distance: 1) hematogenous pathway, due to accidental injection in a vein or venule at the time of implantation; the lungs are the most frequent destination of migration; 2) lymphatic pathway, due to injury of large lymphatic vessels; local lymph nodes are the most common migration destination; 3) phagocytosis of particles by macrophages traveling through the lymphatic system to local lymph nodes. These circumstances can be extrapolated to allogenic particles injected in the orofacial region, where a dense network of lymphatic capillaries and venules drain the oral mucosa and facial skin. In these cases, cervical lymph nodes are the most frequent destination of particle migration. The appearance of a particle migration phenomenon at the time of implantation and development of a fibrous capsule around the injected material have been reported. Nevertheless, the appearance of foreign body granulomas at a distance several weeks after implantation, as in the case presented and previous observations,¹ supports the existence of complex immunological response mechanisms. In any case, the intrinsic mechanisms of foreign body granuloma formation and migration are not completely clear.

Several authors have reported the particle migration phenomenon after the injection of allogenic substances, generally soft tissue fillers, but there have been no previous reports of the migration of foreign body granulomas from plastic polymer particles that have not yet been injected. During patient follow-up, three fundamental points can be established with regard to the location and time of appearance of lesions: 1) right mouth floor one month after treating trismus; 2) right sublingual gland three months post-treatment; and 3) right submandibular region two months posttreatment. All lesions presented a focal histiocytic reaction with giant multinucleate cells and fibrinoid material. Dark colored foreign body particles were demonstrated in all lesions. The patient denied injecting soft tissue filler or undergoing cosmetic procedures in the orofacial region. A direct relation was established between the material of the foreign body particles found in granulomatous foci and the paraphenylendiamine of the appliance used to manage the patient’s trismus during 4 months. During this period, repetitive friction on the occlusal surface of the trismus appliance could have caused small particles to separate and deposit in the gum region and mouth floor. Through the salivary canaliculi and/or periodontal ligament of the adjacent teeth, an indeterminate number of particles could have reached the submucosal region. Capture by macrophages may explain the migration phenomenon and appearance of multiple foreign-body granuloma foci throughout the lymphatic drainage system and cervical lymph nodes. The excisional biopsy of the masses on the mouth floor could have disturbed the integrity of muscular fasciae, thus facilitating particle migration.

The differential diagnosis of multiple nodules or persistent cervico-orofacial inflammation includes several conditions aside from foreign-body granuloma. Some inflammatory diseases have a similar clinical presentation, such as contact dermatitis, facial edema with eosinophilia, cheilitis glandularis apostematosa, and Ascher’s syndrome. Some infectious diseases may debut with persistent lymphedematous inflammation, such as erysipelas, tuberculosis, lepromatous leprosy, South American blastomycosis, and trichinosis. The broad group of orofacial granulomatoses must be considered, and within this group, Crohn’s disease, Melkerson- Rosenthal syndrome, and sarcoidosis. Desmoid fibromatosis and low-grade fibrosarcoma must be considered in aggressive cases and extensive lesions.^3,4 Histological findings may be misinterpreted as eosinophilic angiolymphoid hyperplasia, a rare benign disorder that debuts with intradermal or subcutaneous nodules in the head and neck region. Its appearance in the oral mucosa is, however, extremely uncommon.

The recommended treatment of foreign-body granuloma is surgical resection of well delimited nodular lesions. The surgical treatment of extensive lesions is debated. Some authors claim that the eradication of granulomatous tissue is unlikely and that scar tissue and fistulas will form.⁵ In our opinion, surgery is also the best option in such cases, particularly if we consider that corticoid treatment has shown little or no effectiveness. The least aggressive surgical approach that allows adequate exposure of the lesion should be chosen. Reconstructive surgery should be considered as necessary.

In conclusion, foreign body granulomas may appear in the presence of aluminum silicate particles released by trismus rehabilitation devices. The phenomenon of particle migration from the oral mucosa to cervical lymph nodes can be explained by phagocytosis of the particles by macrophages and their transport through lymphatic vessels in conjunction with local surgical debridement procedures. Future clinical and experimental studies will make it possible to explain many pathophysiological aspects related with particle migration within the context of foreign body granulomas in the orofacial region.

Correspondence:
R. González-García
Hospital Universitario La Princesa
c/ Diego de León 62
28006 Madrid, España

References

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5. Ficarra G, Mosqueda-Taylor A, Carlos R. Silicone granuloma of the facial tissues: a report of seven cases. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2002;94: 65-73.        [ Links ]