経過観察例からみた胃悪性リンパ腫の診断学的問題点と遺伝子検索の有用性

Difficulties of Early Endoscopic Diagnosis and Usefulness of Gene Analysis in the Cases of Primary Gastric Malignant Lymphoma

要旨　1962年から1992年までに当院で得られた原発性胃悪性リンパ腫147例のうち，初回内視鏡検査で確診し得ず経過観察された28例について内視鏡所見，生検病理所見をretrospectiveに検討した.その結果，初回内視鏡検査時，表層性所見のみを示した17例中11例（61％）にcobblestone様所見，褪色調変化が認められ，これらの所見に十分留意し積極的に悪性を疑うことが重要であると考えられた.また，PCR法により免疫グロブリン重鎖遺伝子再構成の検出を試み，悪性リンパ腫8例中7例，88％にB細胞の単クローン性増殖を証明できた.本法は，補助診断として形態診断を補完しうる，極めて有用性の高い検査と思われた.

　Factors of delay in early diagnosis were examined in 28 cases of primary gastric malignant lymphoma (ML) the malignancy of which was not certified at the initial endoscopic examination. Twenty of 28 cases had final diagnosis of ML less than one year after the initial examination, indicating difficulties involved in histological diagnosis by biopsy. In the remaining 8 cases, histological diagnosis of ML by biopsy was made after 1 year or more, and 3 of the 8 cases had been followed up for more than 5 years (10 years and 2 months as the maximum). In spite of the delay in early diagnosis, the depth of invasion was limited to within submucosal layer in most of the cases (22/28: 79%). The observation period in 5 of the 6 advanced cases was less than 6 months, and that of the remaining 1 case was 1 year

　The endoscopic findings of “cobblestone-like appearance” and/or “flossy discoloration” were recognized in more than half of the cases at the initial examination with superficial findings (11/17: 65%), and, more or less, in all of the cases during the follow-up examinations retrospectively, indicating the diagnostic significance of these findings, as reported by Mitsushima et al and Yamaguchi et al. In spite of the presence of these early diagnostic findings, surgery could not be indicated until biopsy revealed the malignancy of the lesions. This is because invasion of ML is usually multicentric and total gastrectomy is recommended. Gene analysis detecting monoclonality of IgH gene can be applied to minimal biopsy specimens by polymerase chain reaction (PCR). The preliminary series using fresh frozen materials clearly revealed correspondence with the final histological diagnosis of reactive lymphreticular hyperplasia (RLH) and ML, as shown in Fig. 1. And in a case closely followed up for 3 months (Case 2 presented), single band formation (presence of monoclonality) of IgH gene was detected from the initial biopsy specimens the histological diagnosis of which was borderline between RLH and ML. Though PCR is not easily applied to formalin-fixed biopsy specimens, single band formation could be detected in one of the 3 cases examined (Case 3 presented). In this case, monoclonality of IgH gene was certified in the biopsy specimens obtained from the second and the final examinations, performed about 2 years and 4 years after the initial endoscopy, respectively, suggesting the change from a benign lesion to a malignant one.

　In conclusion, gene analysis detecting monoclonality of IgH gene from biopsy specimens can be regarded as useful for us to overcome the difficulty of diagnosing gastric ML, particularly those in the early stage.