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口腔組織を構成している上皮組織(口腔粘膜上皮、唾液腺上皮、歯原性上皮)、および唾液腺上皮や歯原性上皮から発症する腫瘍ならびに嚢胞におけるサイトケラチン(pan-CK、CK7、CK8、CK10、CK13、CK14、CK18およびCK19)の発現を免疫組織化学的に検索した結果、CK8、CK14およびCK19は正常上皮、腫瘍実質、嚢胞の裏装上皮のすべてに発現した。しかし、CK7は歯原性上皮と歯原性腫瘍および歯原性嚢胞に発現がなく、それ以外のすべての正常および病変上皮はこれを発現した。CK10は一部の口腔粘膜上皮の角化層付近とglandular odontogenic cyst(GOC)に発現するものがみられた以外はすべて陰性であった。また、CK18も歯原性上皮の一部に極めて弱い発現性を示す例があった。しかし、GOCは例外的に強く発現した。GOCは今回検出の対象としたすべてのサイトケラチンを発現し、他の病変と比べてかなり特殊な病変とみなすことができた。組織学的に、このGOCと類似性の高い顎中心性粘表皮癌は、CK18が非発現であるほかはGOCと同様の発現性を示した。ムチカルミン染色では、正常唾液腺上皮と唾液腺腫瘍に染色陽性を示し、同時にGOCの裏装上皮にも陽性を示した。これらの所見から、口腔を構成する上皮細胞は、すべてがCK8とCK14を基本的な細胞骨格としていこと、その他のサイトケラチンは上皮の種類によって質的(種類)あるいは量的(発現の強さ)に差異を示し、これは分化の違いを反映しているものと考えられた。また、サイトケラチン発現性とムチカルミン染色性から、GOCは粘表皮癌と近縁の病変、あるいは前駆病変の可能性であることも示唆された。More than 20 types of cytokeratins(CKs), which are well known as intermediate filaments of epithelial cells, have been analyzed in various types of epithelial cells. The expression pattern of proteins differs with the kind of epithelium associated with cell differentiation. Therefore, the peculiarity of CK expressions can be applied to the differential diagnosis of neoplasms arising from various types of epithelial cells. To clarify the pattern of cytokeratins in the cells comprising the oral epithelial tissues and lesions originating from various epithelial tissues, we performed immunohitochemical analyses of the expression pattern of CKs(pan-CK, CK7, CK8, CK10, CK13, CK14, CK18, and CK19). Further, we also analyzed the nature of CKs expression and mucicarmine staining to determine the difference between the bony central mucoepidermoid carcinoma(CMEC)arised from mandible and the glandular odontogenic cyst(GOC). CK8,CK14, and CK19 were expressed in the epithelial cells of all specimens in this study. CK7 was expressed in the epithelial cells of normal mucosal and salivary gland, but was not expressed in the odontogenic tumors and odonotogenic cysts epithelia. CK10 was expressed only in a part of oral mucosal epithelium and GOC lining epithelium. However, the intensity of CK10 expression was weak in both types of epithelial cells. The expression of CK18 also showed a tendency to be limited to several types of cells such as salivary gland ductal cells and GOC lining epithelial cells. These findings indicate that epithelial cells in the oral region including those from abnormal tissue express the same CKs, and different sorts of CKs, suggesting that these features of the CK expression dependant on variations in cellular differentiation among the oral epithelium. GOC lining epithelium showed a specific expression pattern that expressed all CKs. It was also peculiar that the expression patterns of CKs in GOC were similar to those of mucoepidermoid carcinoma cells, and both lesions exhibited mucicarmine-positive staining. These findings suggest that these lesions are related to each other and/or GOC is the pre-existing or pre-cancerous lesion of central mucoepidermoid carcinoma.

P(論文), Mucoepidermoid carcinoma, one type of malignant tumor of the salivary glands, is composed of mucous, squamous, intermediate and clear cells, and mainly occurs in the major salivary glands, especially the parotid gland (60%) and in the minor salivary glands (30%). Clinically, mucoepidermoid carcinoma from originating in the salivary gland of palate is rare. We report a study of mucoepidermoid carcinoma which is composed of clear cells, that occured in the center of palate. A 67-year-old male was referred to our hospital because of mass of his palate. The panorama X-ray and the computed tomography clearly showed a monolocular radiolucent lesion. Biopsy specimen was suspected to be a mucoepidermoid carcinoma. We removed the tumor and partial maxilla under general anesthesia. Histologically, the tumor mainly consisted of clear, mucous, squamous cells, and the histopathologic diagnosis was mucoepidermoid carcinoma. The patient's postoperative course has been good, with no evidence of recurrence as of about one and a half years after the operation.

Fifty patients treated for salivary gland tumor in our hospital were clinicopathologically studied for 15 years, from April 1989 to March 2004. The results are as follows: 1. There were 30cases (60.0%) of benign tumors and 20cases (40.0%) of malignant tumors. 2. Salivary gland tumors were equally found in males (25cases; 50.0%) and female (25cases; 50.0%). Benign tumors occurred in slightly more females (16cases; 53.3%) than males (14cases; 46.7%) and malignant tumors were seen in more males (12cases; 60.0%) than females (8cases; 40.0%). 3. The average age of the patients was 52.7 years (benign tumors; 44.8 years old, malignant tumors; 63.3 years old). 4. Pleomorphic adenoma was the most common tumor. It accounted for 52.0% of all tumors and 86.7% of the benign tumors. Adenoid cystic carcinoma had the highest incidence among the malignant tumors (26.0% in all tumors, 65.0% in malignancy). 5. At the first medical examination, while most patients with benign tumor had only swelling without pain, the patients with malignant tumor had swelling with pain and/or ulcer. 6. The period from onset to first hospital visit for benign tumor cases was longer than for malignant tumor cases (5 years 4 months and 8months respectively). 7. Tumor size at first examination was 2-4cm in 27cases (57.4%). 8. Most tumors occurred in the palatal gland (19cases; 38.0%) followed by the submandibular gland (11cases; 22.0%) and finally the parotid gland (6cases; 12.0%). Palatal gland tumors were the most common benign and malignant tumors. 9. In terms of malignancy, more than half the tumors (12cases; 66.7%) were at stageI. 10. Surgical treatment was performed in 16 cases (80.0%) of malignant tumors., 論文

口腔病理学分野の業務の一つである病理組織診断において,これまでに扱った腫瘍および腫瘍性病変は1,493例に上る.余り多い例数とは云えないが,中にはかなりの数の稀少症例があった.その中から,岐阜歯科学会30周年記念誌発刊に因んで,非上皮性腫瘍のspindle cell carcinoma, angiosarcoma, follicular lymphoma, rhabdomyosarcoma, malignant schwannoma,唾液腺腫瘍のpolymorphonous low-grade adenocarcinoma, central mucoepidermoid carcinoma, basal cell adenocarcinoma, clear cell adenocarcinoma, salivary duct adenocarcinoma, myoepithelial carcinoma,歯原性腫瘍のいわゆるodontogenic mixed tumorに属するameloblastic fibrodentinoma, ameloblastic fibro-odontoma, odontoameloblastoma,歯肉に生じたodontomaの計15例を稀少症例として取り挙げた.なお,顎中心性mucoepidermoid carcinomaおよび歯肉のodontomaは,疾患自体は稀少症例ではないが,発症部位が本来,母組織・母細胞の存在しない,いわゆる異所性である点が極めて珍しい疾患である.Spindle cell carcinomaは従来,予後の良いsquamous cell carcinomaのvariantとされてきたが,症例が集積されるに従って,aggressiveで予後不良であることが次第に明らかになってきた.自験例も頚部リンパ節転移がすでに認められ,近年の本腫瘍の概念に当てはまる症例と考えられた.Angiosarcomaは軟組織において比較的発症頻度の高い腫瘍であるが,口腔領域では(良性)血管腫の好発部位であるにも拘らず,その悪性型は極めて稀である.自験例は前歯部歯肉に小腫瘤として発見されたもので,病理組織検索で初めてangiosarcomaであることが判明した.組織像は多くの血管形成という点では高分化の傾向を示したものの,腫瘍細胞の多くは異型性が強く,この面からは高悪性型であることが明らかであった.いずれにしても歯肉には転移性angiosarcomaが多く,自験例のような原発性は極めて稀である.Lymphomaは口腔領域に原発することは稀であるが,稀少症例とは云い難い.しかし,その中のfollicular lymphomaの口腔原発は極めて稀である.自験例は病理組織学的検索によってまずfollicle形成性のリンパ節病変であることが明らかにされたが,病巣にmantle zone, popcorn細胞,lacunar細胞等を混じていた為に,さらに免疫組織化学的検索およびflow cytometryを加えて,mantle cell lymphomaやHodgkin lymphoma等との鑑別を詳細に行い,顎下リンパ節原発のfollicular lymphomaと最終診断された.なお本症例はすでに深頚リンパ節に系統的転移を起こしつつあって,この点も稀な症例であることを示していた.Rhabdomyosarcomaも他部に多く口腔に稀である.自験例は病理組織学的には,ブドウ状型から多形型に至るrhabdomyosarcomaのすべての特徴を有し,電顕的にもまた免疫組織化学的にも横紋筋細胞由来の腫瘍であることが明かであった.これら所見を総合して混合型と判断したが,口腔の本腫瘍のほとんどは胎児型であって混合型は極めて少ない.Malignant schwannomaは現在malignant peripheral nerve sheath tumors (MPNSTS)に包含されている.かつては軟部腫瘍の代表的腫瘍と見なされてきたが,今日,ほとんどがvon Recklinghausen病に由来する極めて稀な腫瘍とされている.自験例は耳下腺後部に発生し臨床的にpleomorphic adenomaと診断,剔出されたが,病理組織学的には, verocay小体やpalisade appearanceを示すAntoni A型を主成分として,さらにAntoni B型の混在する典型的なschwannomaの組織像を示し,それぞれの細胞に強い異型性を認め,malignant schwannomaであることが擦断的であった.加えて自験例はvon Recklinghausen病とは関係なく原発性であり,この点からも稀少症例中の稀少症例とみなし得た.Polymorphous low-grade adenocarcinomaは近年WHOで独立した腫瘍として分類・命名された唾液腺腫瘍の一つであり,その定義や組織像あるいは鑑別すべき他腫瘍を見ると,とくに従来のpleomorphic adenomaと診断されてきた中に本腫瘍とすべき症例が多いように思われる.本大学の過去の症例も再度検索した所,只一例に本腫瘍とすべき例があった.Central mucoepidermoid carcinomaは腫瘍そのものは別としてその発生部位が特異的で,この点に関する限り稀少症例である.自験例はX線診査によって歯原腫瘍と見なされたが,剔出物は明らかに中悪性型のmucoepidermoid carcinomaの組織像を示した.組織発生については,嚢胞から生じたことが明らかな発芽状の細胞増殖とその先端のmucoepidermoid carcinomaの性格を示す組織分化を認め,この所見から,いわゆるmucoepidermoid odontogenic cystに由来する腫瘍と考えられた.Basal cell adenocarcinomaはmiscellaneous carcinomaの一つで,これもまた極めて稀少であるが,自験例は基底細胞様の細胞が充実性且つ索状,浸潤性に増殖し,その中にわずかながら腺由来を想わせる管腔形成や粘液細胞が混じていた.Clear cell adenocarcinomaと診断した自験例は,上顎洞から眼窩部,篩骨洞,鼻腔にまたがる広範な増殖を示した腫瘍で,腫瘍細胞の細胞質のほとんどが淡明で,epithelial-myoepithelial carcinomaのmonomorphic型を示した.Salivary duct adenocarcinomaはcribriformを呈する悪性腫瘍で,adenoid cystic carcinomaと誤診し易いが,精査すると管腔形成の様相がかなり異なり,また,comedo carcinomaに類似する管腔形成をも認める.自験例は明確なcomedoの像はなかったが,いわゆるcribriform ductal carcinomaに類似する所見を示した.Myoepithelial carcinomaはmalignant pleomorphic adenoma等との鑑別が容易ではない.その中にあって診断の根拠とされるのは(1)spindle, plasmacytoidあるいはpolygonal epithelioid cellの増殖,(2)管腔形成がわずかであること,(3)筋細胞に特異的タンパクの発現の三項目である.我々はこれまでにこれら条件を充たす症例を二例経験した.Ameloblastic fibrodentinomaは現時点でも少数例しか報告されていない極めて稀な腫瘍である.自験例は前歯部から小臼歯部にかけて増大したものである.病理組織的には増殖した線維組織や粘液組織の中に,歯原上皮の胞巣状増殖と,その胞巣付近の象牙質様組織の形成より成り,象牙質様組織の周囲に象牙芽細胞様細胞の分化をも認めた.本腫瘍は往々hyperplastic dental follicleとも見間違えるが,dental follicleの場合は石灰化物は象牙質様ではなく,その周囲に細胞の分化をも認めない.Ameloblastic fibro-odontomaも50例を越える報告はない.自験例は下顎第二大臼歯から下顎枝にかけて生じ,生検時にはameloblastic fibromaと診断されたが,剔出物は歯乳頭に似た組織の中に索状や濾胞状の歯原上皮細胞が増殖し,さらに大小の歯牙様石灰化物の形成を伴い,明らかにameloblastic fibro-odontomaと診断すべき例であった.Odontoameloblastomaも極めて稀な侵襲性の腫瘍で,犬歯部から後方にかけて生じるという特徴がある.自験例も下顎犬歯部から第二小臼歯にかけて生じ,X線診査で多くの歯牙様の不透過物を認めた.病巣は歯の形成を伴う歯原上皮の索状や充実性増殖を示し,幼若なodontomaと類似する所見を示した.しかし,歯原上皮は退化性ではなく明らかに腫瘍性のパターンを示していた.Hard odontomaそのものは発症頻度が多いが,歯肉に異所性に生じるものは少ない.自験例は皮質骨内に生じたimmature odontomaが皮質骨の一部を破って歯肉にまで及んだ極めて稀な症例である.以上のいわゆるodontogenic mixed tumorは,それぞれが独立した腫瘍か,あるいはameloblastic fibromaからhard odontomaに至る過程の一連の腫瘍かが今尚論議されている.そこで今回,これら貴重な症例を得たのを機に,この論議の解決の一助をなすべく免疫組織化学的検索をも加えて臨床病理学的検索を試みた.そしてcellular-fibronectinやamelogeninを中心とする発現性の違い,発症年齢や発症部位の差違等を総合して,ameloblastic fibrodentinoma, ameloblastic fibro-odontoma, odontoameloblastomaおよびodontomaはそれぞれ独立した腫瘍あるいは腫瘍性病変であるという結論に達した., For the memorial publication of the Gifu Dental Society, we report rare tumors and/or tumor-like lesions, that were selected from 1,493 cases in patients who had undergone surgical resection at the School of Dentistry, Asahi University.The following categories of tumors were selected for the present report: non-odontogenic tumors (spindle cell carcinoma, angiosarcoma, follicular lymphoma, rhabdomyosarcoma, and malignant schwannoma), salivary gland tumors (polymorphous low-grade adenocarcinoma, central mucoepidermoid carcinoma, basal cell adenocarcinoma, clear cell adenocarcinoma, salivary duct adenocarcinoma, and myoepithelial carcinoma), and odontogenic mixed tumors (ameloblastic fibrodentinoma, ameloblastic fibroodontoma, odontoameloblastoma and hard odontoma in the gingiva).Histopathologic examination of spindle cell carcinoma showed proliferation of spindle-shaped epithelial cells and fibroblastic cells in the gingiva, and it had metastasized to the deep neck lymph nodes in our patient. The metastasized tumor was an epidermoid carcinoma with high keratinization. These findings indicate that spindle cell carcinoma is particularly aggressive.Non-epithelial tumors, i.e., angiosarcoma, rhabdomyosarcoma and malignant schwannoma, develop in many organs of the body. However, such tumors rarely develop in the oral region. In particular, angiosarcoma and malignant schwannoma in the oral region are extremely rare.Primary angiosarcoma in the oral region tends to arise in the tongue, lip, parotid gland and submandibular gland. Comparing with angiosarcoma arised in such portion, the gingival lesion is known to be metastasized sarcoma from other area. However, our patient with angiosarcoma clearly had a primary tumor in the gingiva. Therefore, it could be regarded as a rare case.Primary follicular lymphoma in the oral region is also very rare. Our patient had primary follicular lymphoma that had arisen in the submandibular lymph node, with chronic sialoadenitis. Although this type of lymphoma exhibits comparatively slow growth, it had metastasized to the deep neck lymph nodes in our patient.Rhabdomyosarcoma in the oral region is also rare. If this sarcoma arises in the oral region, the tumor generally shows the fetal type. Our patient, however, was given the diagnosis of mixed type rhabdomyosarcoma based on histological features of the tumor showing embryonal, alveolar and undifferentiated patterns.Malignant schwannoma generally originates in the lesions of von Recklinghausen's disease, and the development of malignant schwannoma in patients who do not have von Recklinghausen's disease is extremely rare. The malignant tumor of our patient clearly showed features of schwannoma in that it consisted of two components, Antoni A and B type. The tumor cells in both components showed various patterns of cellular irregularity, especially nuclear irregularity in the size, hyperchromatism and mitosis. Further, the tumor was obviously a primary lesion based on its clinical characteristics, and therefore these aspects also indicated that this tumor is very rare.Polymorphous low-grade adenocarcinoma has been recognized as a category of salivary gland tumors since 1983. A tumor that is very similar to polymorphous low-grade adenocarcinoma is pleomorphic adenoma and adenoid cystic carcinoma. Thus, we reexamined those cases that had been given the diagnosis of both adenoma and adenocarcinoma, and among these cases, we re-assigned the diagnosis of only one case as polymorphous low-grade adenocarcinoma.Central mucoepidermoid carcinoma is extremely rare. Our case occurred in the mandible, and histologically, the tumor showed the typical structure of mucoepidermoid carcinoma in that it consisted of three types of cells: mucin-secreting cells, squamous cells and intermediate cells. In our patient, these cells could be regarded as having originated from the large cyst in the mandible. The structures that had formed by budding from the cyst, were very similar to the nests in a mucoepidermoid odontogenic cyst.Basal cell adenocarcinoma, which is one of the miscellaneous carcinomas, is quite rare among salivary gland tumors. Recognition of this adenocarcinoma hinges on the following: it is an infiltrative tumor with the histomorphology of basal cell adenoma. These tumors have a greater degree of nuclear pleomorphism and a higher mitotic count than other tumors. The histological features of our case, which occurred in the palate met the diagnostic criteria for basal cell adenocarcinoma.Clear cell adenocarcinoma is also a miscellaneous carcinoma, and is infrequently encountered. In our patient, the adenocarcinoma had invaded over the facial bones, and histopathologic examination revealed solid proliferation of clear cells with features of the monomorphic type of epithelial-myoepithelial carcinoma.Ameloblastic fibrodentinoma, ameloblastic fibro-odontoma and odontoameloblastoma, which are classified as tumors of the odontogenic epithelium with odontogenic ectomesenchyme are extremely rare. We encountered one case of each of the three types of tumors, and attempted to clarify whether the three types of tumors are the same tumor entity or if they are distinct tumor entities by clinicopathological and immunohistochemical analyses. Various data obtained from these analyses, especially the results of immunohistochemical analysis for cellular-fibronectin, PCNA and amelogenin expression in the odontogenic epithelium, indicated that ameloblastic fibrodentinoma, ameloblastic fibro-odontoma and odontoameloblastoma have different natures and can be considered as three separate tumor entities.