Benign Fibrous Histiocytoma Occurred in the Alveolar Mucosa

Oral Oncology EXTRA (2005) 41, 253–258

http://intl.elsevierhealth.com/journal/ooex

CASE REPORT Benign ﬁbrous histiocytoma occurred in the alveolar mucosa accompanying with sialidosis type 2 in Japanese infant

Miyoko Hidaka a,*, Akihiro Yamashita a, Kouzou Sakamoto a, Ken-ichi Mukaisho b, Takanori Hattori b, Gaku Yamamoto a a Department of Oral and Maxillofacial Surgery, Shiga University of Medical Science, Seta-tsukinowa-cho, Otsu, Shiga 520-2192, Japan b Department of Pathology, Shiga University of Medical Science, Seta-tsukinowa-cho, Otsu, Shiga 520-2192, Japan

Received 9 March 2005; accepted 9 March 2005

KEYWORDS Summary Benign fibrous histiocytoma with sialidosis which is a rare metabolic dis- Gingival histiocytoma; order resulting from the deficiency of a lysosomal enzyme, and a-neuraminidase, as Sialidosis; one of lysosomal storage diseases. The patient; male infant (2 years and 8 months), Cytoplasmic vacuole; with infantile form of sialidosis type 2, shows extensive gingival enlargement and Immunohistochemistry; gingival tumor with a painless mass (4 · 2 · 2 cm), which grew gradually on the gin- Electronmicroscopy giva of left maxillary deciduous molar region. A tumorectomy was performed to improve the mastication. The surgical specimen had many histiocytes positive for CD68 with cytoplasmic vacuoles, which is a specific feature in the patient of glycoprotein degradation disorder. These histiocytes were also positive for lysozyme. The gingival tumor was diagnosed as benign fibrous histiocytoma. The present report is discussed glycoprotein degradation disorder accompanying with gingival hyperplasia. c 2005 Elsevier Ltd. All rights reserved.

Introduction

Sialidosis is classiﬁed as one of lysosomal storage diseases, and it is extremely rare glycoprotein deg- * Corresponding author. Tel.: +81 77 548 2352; fax: +81 77 548 2347. radation disorder (mucolipidosis I) occurring for E-mail address: [email protected] (M. Hi- deﬁciency of the a-neuraminidase; N-acetyl- daka). neuramine acid hydrolase (E.C.3.2.1.18) activity.

Human neuraminidase and b-galactosidase exist in a complex with a 32-KD glycoprotein in lysosomal body. The former protein was found to have a dual function: it is required for the aggregation of monomeric 64-KD b-galactosidase into high molecular weight (600–700KD) multimers and it is an essential subunit of neuraminidase together with a 76-KD polypeptide.1 Defects in neuraminidase activity show clinical phenotypes.2–8 It has been reported that the deﬁ- ciency of the primary neuraminidase activity as sialidosis and sialidosis was divided into two distinct types: the type 1—a group with normal physical appearance and body proportions, cherry-red spots, myoclonus; and the type 2—a dysmor- phic group with short stature and bony abnormalities.9 It is further divided the type 2 disease into infantile and juvenile sialidosis. Later, Young et al.10 added yet another category, desig- nated congenital sialidosis, to the type 2 subgroup. The paper deals with a case of the gingival benign ﬁbrous histiocytoma of the patient diagnosed as an infantile form of sialidosis type 2, and also discussed with cell biological features in lysosomal storage disease.

Case report

A male patient (2 years and 8 months) complaining of swollen gums and a painless mass on the gingiva was referred to our hospital. In familial history, his mother is a mentally deficient and his father is her uncle. He had previously been diagnosed as sialidosis by the Laboratory evidence of deficiency of the glycoprotein a-neuraminidase activity and normal b-galactosidase activity in the peripheral leuco- cytes. The observation of general global develop- mental delay and facial specific features confirmed the diagnosis as infantile form of sialidosis type 2. Extraoral examination showed obvious develop- Figure 1 (A) Full face showing typical facies of siali- mental delay; (1) arms and legs were edematous, dosis. (coarse facial feature, front part protrusion, (2) typical facies seen in sialidosis type 2 were swelling of eyelid, saddle nose and long philtrum). (B) present: coarse facial feature, front part protru- The tumor measuring 4 · 2 · 2 cm is detected in a left sion, swelling of eyelid, saddle nose and long phil- side maxilla deciduous at preoperation. trum (Fig. 1A). Intraoral examination revealed massive gingival hyperplasia, a painless mass in the gingiva in left The patient could not close the mouth com- maxillary deciduous molar region and erupted pletely and he had a disturbance of food intake. lower anterior teeth. It had grown gradually and A tumorectomy was performed to improve the the mass showed 4 · 2 · 2cminsize(Fig. 1B). Upon mastication. The healing of wounded area was palpation, the gingival tissues were flabby and good and the feeding condition was improved. In slightly elastic. The tongue was thick but relatively postoperative 4 months he showed aggravation of normal in appearance and lower 4 primary incisors general condition and a recurrence of a tumor had partially erupted. mass. Afterwards the patient died of sudden Benign fibrous histiocytoma with sialidosis type 2 in Japanese infant 255 laryngismus paralyticus and dyspnea by thoracic tissue. Multinucleated giant cells of touton type compression by pleural effusion, pulmonary edema laid scattered in connective tissue (Fig. 2A). Many and ascites. histiocytes were positive for CD68 (KP1, 1:100, DAKO, Glostrup, Denmark), and had cytoplasmic vacuoles in these histiocytes (Fig. 2B). Also these histiocytes were positive for lysozyme (Lyso- Pathological findings zyme, 1:100, DakoCytomation, California, USA). Lysozyme was present chiefly in granular intrecyto- The gingival tumor tissue revealed that covered plasmic of histiocytes (Fig. 2C). Staining nuclei of epithelium erosion, and it showed macrophages tumor cells were a few for Ki67 (MIB-1, 1:100, and fibrous histiocytic cell infiltration in connective DAKO) (Fig. 2D) and cells were without marked

Figure 2 Histological findings in the gingivectomy specimen. (A) HE, (B) CD68, (C) Lysozyme, (D) Ki67, (E) CD45, (F) CD34. (A) It showed many histiocytes and fibrous histionic proliferation. Inset: Higher magnification of touton type multinucleated giant cell. (B, C) Many histiocytes were positive for CD68 (B) and lysozyme (C). (D) Several cells in the basal cell layer of gingiva were positive for Ki67. However, Ki67 positive cells were quite rare in this tumor. (E, F) There were no histiocytes positive for CD45 (E) and CD34 (F). 256 M. Hidaka et al. atypia. On the other hand, the tumor cells were Discussion negative for CD34 (NU-4A1, 1:100, Nichirei, Tokyo, Japan) (Fig. 2E), CD31 (JC/70A, 1:100, DAKO), S- Sialidosis is belong to lysosomal storage diseases 100 (S-100, 1:100, Nichirei), a-SMA (1A4, 1:100, for deficiency of a-neuraminidase activity in lyso- Dako corporation, CA, USA), and HMB-45 (HMB45, some. Lysosomal storage diseases are classified 1:100, Dako corporation). So it was diagnosed as into glycogenosis, mucopolysaccharidoses, lipido- benign fibrous histiocytoma. Many lymphocytes ses, glycoprotein degradation disorders (mucolipi- were positive for CD45 (4KB5, 1:100, DAKO) dosis) and others according to the stored and most of them had cytoplasmic vacuoles substrates by stromal modality or a kind of a (Fig. 2F). deficient enzyme. Disorders as sialidosis, I-cell disease, and aspartylglycosaminuria are included in this mucolipidosis.11 The normal turnover of glyco- Electron microscopic finding proteins that originate from cytoplasm, cell sur- face and extracellular matrix, occurs in We used small pieces of paraffin embedding tumor lysosomes.12 The deficiency of such enzymes tissue after deparaffinigation. They were fixed with responsible for this lysosomal turnover of glycopro- 2.5% glutaraldehyde in phosphate buffered saline teins causes incomplete degradation of N-glycosid- (PBS) and postfixed with 2% osmium tetroxide in ically linked oligosaccharides, and results in PBS, and the specimens were embedded in Epon accumulations of these oligosaccharides in the following dehydration. Ultrathin sections stained lysosomes.13 Cytoplasmic vacuoles are caused by with 2% uranyl acetate in methanol and lead sul- the swollen lysosomes. In glycoprotein dysbolism fate, and examined under a Hitachi H-700 electron patient vacuolated lymphocytes in peripheral microscopy (model H-700 electron microscope, blood are found with high frequency.9 The cyto- Hitachi, Japan). Electron microscopic features re- plasmic vacuole is also detected in cells of the skin, vealed many cytoplasmic vacuoles in histiocytes liver and other organs. It is indispensable to do a (Fig. 3A) and lymphocytes (Fig. 3B). tissue biopsy for a child of congenital metabolic

Figure 3 Transmission electron microscope image. (A) TEM · 6000, (B) TEM · 4000. Cytoplasmic vacuoles were seen in the histiocytes (A), and in the lymphocytes (B). Benign fibrous histiocytoma with sialidosis type 2 in Japanese infant 257 disease to accept such a special cell. Bonnaure- which is lysosomal proteolytic enzymes, show gin- Mallet et al.14 reported that gingival biopsy is easily gival enlargement. Active block of the cathepsin- performed, is non-iatrogenic, leaves nor scar, and L caused gingival enlargement to be found in I-cell could be properly used to help diagnose metabolic disease. Complete loss of cathepsin-L function diseases in children. Taylor and Shuff15 reported results in the development of gingival overgrowth. that the identification of the oral abnormalities Taken together, there could be correlation with make an important contribution to the diagnosis resisting glycoprotein degradation disorder and gin- of the fatal condition. They appealed for magni- gival hyperplasia. It is suggested that lowered tude of a gingival biopsy together. In the present activity of lysosomal enzymes is responsible for case, we could also detect histiocytes and lympho- gingival hyperplasia as seen in the present case, cytes with cytoplasmic vacuolar degenerations, and that insufficient protein digestion results in which is specific feature of glycoprotein degrada- the excess accumulation of proteins in intercellular tion disorder, from intraoral tissue. In the present spaces. case, many histiocytes positive for CD68 and many The present report is the first description of a lymphocytes positive for CD45 have cytoplasmic patient with sialidosis who had benign fibrous histi- vacuoles. These histiocytic cells showed positive ocytoma of the gingiva. This rare case report may reaction for lysozyme. Lysozyme (molecular weight signify a pathogenic mechanism of gingival 14,000 Da) is a bacteriolytic enzyme and has been overgrowth potentially related to the lysosomal used as immunohistochemical markers for histio- enzymes, glycoprotein a-neuraminidase. cytic cells and to test and prove the histiocytic ori- gin of tumors, such as benign and malignant fibrous histiocytomas.16 Moreover lysozyme is not detected in the cytoplasm of neoplastic cell in Acknowledgments non-fibrohistiocytic tumors.17 In the present case, histiocytic cells were without marked atypia and The authors wish to thank Mr. T Yamamoto in Ki67 positive cells are quite rare. 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