Kim 2009
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This case report describes a patient who developed a gingival swelling after undergoing endodontic treatment of his lower left canine tooth. During the treatment, an intracanal medication (Calcipex II) was overfilled into the periapical area. A biopsy of the swelling revealed a foreign body granuloma containing macrophages that had engulfed fine granules of the Calcipex II material. The granules had dispersed widely into the surrounding tissues rather than remaining localized. Immunohistochemistry showed the granule-laden cells were macrophages, not neutrophils, and they appeared to be undergoing apoptosis. This represents the first reported case of a foreign body reaction induced by overfilling of the Calcipex II calcium hydrox
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Kim 2009
- 1. Overfilling of calcium hydroxide– based paste Calcipex II produced a foreign body granuloma without acute inflammatory reaction Jin Woo Kim, DDS, PhD,a Kyung Mo Cho, DDS, PhD,a Se Hee Park, DDS, MSD, PhD,a Seung Gon Song, DDS,a Mi Sun Park, DDS,b Hye Rim Jung, DDS,b Ji Yong Song, BS,b Yeon Sook Kim, DDS, PhD,b and Suk Keun Lee, DDS, PhD,b Gangneung, Korea COLLEGE OF DENTISTRY, KANGNUNG NATIONAL UNIVERSITY A patient, a 62-year-old man, received endodontic treatment of the lower left canine complicated by apical overfilling of Calcipex II. At the second day after the root canal filling, the 14th day after placement of Calcipex II intracanal medication, he complained of a gingival swelling in the treated area. The incisional biopsy of the gingival swelling revealed a foreign body granuloma infiltrated with macrophages engulfing the fine Calcipex II granules but with polymorphonuclear leukocytes (PMNs). However, the gingival swelling was healed uneventfully, and the tooth was free of symptoms at 4 months’ follow-up. This study first reports the Calcipex II–induced reaction in human periodontium. In the immunohistochemistry using antisera of lysozyme, CD31, CD68, interleukin-8 (IL-8), and poly(ADP-ribose) polymerase 1 (PARP-1), the granule-laden cells are positive for lysozyme, CD31, CD68, and PARP-1, but negative for IL-8. Thus, it is presumed that the granule-laden cells belong to the macrophages/monocytes rather than the PMNs, and that they gradually undergo the apoptotic processes. These data suggest that the canal dressing material, Calcipex II, is able to be widely dispersed into the periodontal tissues, primarily engulfed by macrophages, and resulted in the foreign body granuloma in the absence of acute inflammatory reaction. (Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2009;107:e73-e76) CASE REPORT through the apical foramen (Fig. 1, b). On the third visit, the A 62-year-old man was referred from a private dental clinic working length of the root canal was recalculated and the to the Department of Conservative Dentistry in Kangnung apical preparation enlarged to size #55. A root canal filling National University (KNU) Dental Hospital. The chief com- with gutta-percha cone and AH-26 sealer (DeTrey/Dentsply, plaint was vestibular swelling in the lower left canine (#22) Konstanz, Germany) was placed. The root canal was well area. The patient’s dentomedical history was noncontributory. obturated, and the overfilling of Calcipex II was reduced in Pulp test revealed that tooth #22 was unresponsive to cold and amount (Fig. 1, c). electric pulp testing, whereas the adjacent teeth responded At the day after the root canal filling (the 14th day after within normal limits. The tooth was very sensitive to percus- Calcipex II placement), the patient came back complaining of sion and palpation. Pus was discharged from the labial gin- a gingival swelling in the area of tooth #22 (Fig. 1, d). The gival sulcus of the tooth. Purulent exudate was also noted on gingival swelling showed no pus discharge in the gingival access opening of the tooth. The root canal was irrigated with sulcus, and the tooth was not tender to touch. An incisional 3% sodium hypochlorite and 2% chlorhexidine in conjunction biopsy was done and the specimen fixed in 10% neutral with root canal instrumentation after radiographic determina- formalin. The biopsy was subsequently embedded in paraffin, tion of root canal length (Fig. 1, a). and sectioned in 4 m thickness. The usage of the biopsy On the second visit, the exudates and swelling had de- specimen filed in the Department of Oral Pathology, KNU creased and Calcipex II (Nishika, Shimonoseki, Japan) was Dental Hospital, was approved by the Life Ethics Committee used as an intracanal dressing as suggested by the manufac- of KNU. The histologic sections were routinely stained with turer. The Calcipex II was, however, slightly overfilled hematoxylin and eosin, and also used for immunohistochem- istry using antisera of lysozyme, CD31, CD68, interleukin-8 (IL-8), and poly(ADP-ribose) polymerase 1 (PARP-1) (Santa Supported by research grants from the Korean Science and Engineer- Cruz Biotechnology, Santa Cruz, CA). In addition, the Cal- ing Foundation (R11-2002-001-03003-0 and R01-2003-000- cipex II material was dispersed in water and smeared on glass 10891-0) and the Korean Research Foundation (KRF-2007-013). slide for the microscopic observation. Every microscopic a Department of Conservative Dentistry. image was recorded with a digital camera (Olympus DP-70, b Department of Oral Pathology. Tokyo, Japan). Received for publication Jul 9, 2008; accepted for publication Oct 21, 2008. The microsections of the gingival swelling showed a gran- 1079-2104/$ - see front matter ulomatous lesion heavily infiltrated with fine granular mate- © 2009 Mosby, Inc. All rights reserved. rials, engulfed mostly by macrophages and slightly by stromal doi:10.1016/j.tripleo.2008.10.019 fibroblasts (Fig. 2, a, 1-3). The Calcipex II granules were not e73
- 2. OOOOE e74 Kim et al. March 2009 Fig. 1. Standard radiographs during the endodontic treatment of the lower left canine. a, X-ray for initial working length determination. b, On the second visit, Calcipex II was overfilled into the periapical area (arrows). c, After root canal filling, some Calcipex II remained periapical but reduced in amount (arrows). d, At the second day after canal filling, when the gingival swelling occurred, the canal filling looked fine and there was no change in periapical area (arrows). localized in the granuloma lesion but gradually dispersed root canal is filled in a single-session treatment.1-3 across the border of the granuloma into the adjacent connec- Calcipex II is a calcium hydroxide water-based paste tive tissue (Fig. 2, a, 4 and 5). The fine granular materials for root canal dressing, which is easy to handle and the were identical to the Calcipex II granules smeared on the most easily removed. Great care had to be taken to glass slide, exhibiting slightly translucent and fine granular avoid extrusion via the apical foramen compared with aggregation but no calcification or polymerization (Fig. 2, b). The Calcipex II granules were mainly engulfed by macro- the silicon oil– based Vitapex.4 In the present study, the phages, and also slightly localized at the cytoplasms of fibro- Calcipex II used as an intracanal dressing material was blasts. Still a lot of the fine Calcipex II granules were freely overfilled into the periapical area, and its fine granular dispersed in the stromal fibrous tissue, but rarely in the lumen materials were rapidly migrated up through the gingival of capillaries. In the immunohistochemistry using antisera of tissue. The Calcipex II granules were not calcified nor lysozyme, CD31, CD68, IL-8, and PARP-1, the Calcipex II polymerized in the gingival tissue; rather, they were granule–laden cells were positive for lysozyme, CD31, and diffusely scattered throughout the collagenous fibrous CD68, indicating that the cells belonged to the lineage of tissue, were rapidly engulfed by the macropahges, and macrophage/histiocyte/monocyte and were in the apoptotic resulted in a foreign body granuloma. The granuloma processes (Fig. 2, c-e). On the other hand, the Calcipex II granule–laden cells were negative for IL-8, which is a che- was mainly infiltrated with macrophages, and only a mokine usually positive in neutrophils (Fig. 2, f), similar to few lymphocytes were found, but exclusive of PMNs. the negative control staining (Fig. 2, h). Under the micro- In the immunohistochemistry, the Calcipex II granule– scopic observation in routine hematoxylin and eosin stain, the laden cells were strongly positive for lysozyme, CD31, macrophages filled with the Calcipex II granules could not and CD68, which are markers for the macrophages, readily dissolve the fine granules; rather, they were gradually including histiocytes and monocytes,5-11 whereas they destroyed by the rupture of their cell membrane. Nevertheless were negative for the antibody of IL-8, which is a there appeared no acute inflammatory reaction. The Calcipex marker for PMNs.12 However, the inflammatory degen- II–laden macrophages were strongly positive for PARP-1, indicating that the cells were undergoing the apoptotic pro- eration or necrosis by cytotoxic chemokine IL-8 was cesses, possibly due to the overload of Calcipex II (Fig. 2, g). not observed in the Calcipex II–induced foreign body Eventually, the Calcipex II induced a foreign body granuloma granuloma. by macrophages, but no acute inflammation by PMNs. The Calcipex II granules were too small, 500 nm, to be localized in the root canal, so that they were easily DISCUSSION overflowed and dispersed into the periapical tissues The use of a calcium hydroxide– based intracanal depending on the dynamic pressure that occurred dur- dressing is important for periapical repair in teeth with ing canal filling and biting. The fine Calcipex II gran- periapical lesion. Dressing with calcium hydroxide ules were rapidly engulfed by macrophages and even paste results in better periapical repair than when the endocytosed by stromal fibroblasts. However, the Cal-
- 3. OOOOE Volume 107, Number 3 Kim et al. e75 Fig. 2. Photomicrographs of the Calcipex II-induced foreign body granuloma. a, Hematoxylin and eosin stain. a1, Low magnification of main lesion: The Calcipex II granules were diffusely observed in the stromal cells. a2-a5, High magnification. a2, Most of the Calcipex II granules were engulfed by macrophages (arrows), only a few lymphocytes (arrowheads) were infiltrated but not PMN. a3, Some Calcipex II granules were also endocytosed by stromal fibroblasts (arrowheads); no Calcipex II granules were found in the lumen of capillaries (C). a4, Note the massive dispersion of the Calcipex II granules in the fibrous connective tissue; many Calcipex II granules were found in the cytoplasms of fibroblasts (arrowheads). a5, Border area between the fibrous connective tissue and granulomatous lesion. The Calcipex II granules were diffusely dispersed; note many macro- phages infiltrated into the border area. b, Calcipex II paste smeared on the slide glass. b1, Low magnification: The Calcipex II granules were well dispersed and aggregated (arrows). b2, High magnification: The fine granules of Calcipex II was very small, measuring 500 nm in diameter. c-g, Immunohistochemistry. c, Lysozyme antibody, positive in the Calcipex II granule–laden cells (arrows). d, CD31 antibody, positive in the Calcipex II granule–laden cells (arrows). e, CD68 antibody, positive in the Calcipex II granule–laden cells (arrows). f, Interleukin-8 antibody, negative in the Calcipex II granule–laden cells (arrows). g, Poly(ADP-ribose) polymerase 1 antibody, positive in the Calcipex II granule–-laden cells (arrows). h, Negative control stained without antisera.
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