Qin Zhou, Tian-Rong Xu, Qin-He Fan, Zou-Xung Zhen, Department of Pathology, the First Affiliated Hospital of Nanjing Medica l University, Nanjing 210029, Jiangsu Province, China
Dr. Qin Zhou, female, born in 1960-07-29 in Xuzhou, Jiangsu Provi nce, graduated from the Shanghai Second Medical University with Master degree in 1990, associate chief, Department of Pathology, with twenty-three papers publi shed.
Supported by the Natural Science Foundation of Jiangsu Province Educati on Commission, No.(Educ.)94051.
Correspondence to: Qin Zhou, Department of Pathology, the First Affiliated Hospital of Nanjing Medical University, 300 Kwuangzhou Road, Nanjing, 210029, China
Telephone: +86-25-3718836 Ext. 6445, Fax. +86-25-3724440
Email.Pathojph＠jlonline.com
Received: 1999-05-25 Accepted: 1999-09-13

Subject headings: lymphoma/pathology; intestinal neoplasms/pa thology; intestinal neoplasms/diagnosis

Zhou Q, Xu TR, Fan QH, Zhen ZX. Clinicopathologic study of primary intestinal B cell malignant lymphoma.
World J Gastroentero, 1999;5(6):538-540

INTRODUCTION
Primary intestinal B cell lymphoma is one of the most common extra-nodal lympho mas, which includes two types: intestinal mucosa-associated lymphoid tissue lym phoma (IMALToma) and lymphomatous polyposis (LP). Both have characteristic patho logic features, immunophenotypes and biological behaviors. In this articl e, twenty-five cases were retrospectively analyzed with regard to criteria of d iagnosis and clinicopathologic characteristics.

MATERIALS AND METHODS
Methods
All 25 tissue specimens obtained from surgical operation, were embedded in paraf fin, sectioned and stained by haematoxylin-eosin and immunohistochemical stains (ABC method). The first antibody (CD₂₀, CD₄₅, CD_45R0, CD₆₈, CD₃₀, K, λ, IgG, IgM, IgA, IgD and bcl-2), second an tibody and ABC Kit were produced by Dako and Vector Co.PBS buffer solution was substituted for the first antibodies as the negative control, whereas the lympho ma cases were used for positive control.

Clinical data
There were 21 cases of IMALToma, in which 16 were males and 5 females, age range d 9-70 years, mean age 39.6 years. Location of tumors, 10 were situated in ileu m, 2 at jejunum, 6 in colon, 1 at rectum and 2 in both ileum and colon; there were 4-cases of LP, 3 men and 1 woman, age 30-47 (average 38.8) years, all were l ocated at the terminal ileum. Clinical manifestations of IMALToma were similar t o LP with abdominal pain and mass, melena and mucous stool, intestinal intussece ption and intestinal obstruction, fever, loose bowel movement.

Pathological data
Macroscopically, the IMALToma could be categorized into mushroom, constrictive and ulcerative types; the size of tumor varied from 2cm×1cm×1cm to 20cm×10cm×3.5cm. Sixteen cases had single nodule, five were multiple. The lymphomatous cells infiltrated in the mucosa, sub-mucosa and muscular layer diffusely or focally. Lymphoid follicles were seen in 7 case s. In 9 cases, the germinal centers were partly or entirely replaced by lymphoma cells. Dendritic cells and macrophages with chromophilic bodies disappeared. Th is phenomenon is called follicular colonization (FC). 9 cases showed lymphoepith elial lesion (LEL) in which there were clusters of lymphomatous cells infiltrate d focally at the surface epithelium and/or glands (Figure 1). The glandula r epithelia were destroyed. The neoplastic cells presented a serial cell lineag e of small lymphocyte, centrocyte-like cell (CCL), monocyte-like B cell (MCB) and ly mphoplasma cell (LPC), and also centroblast like cells (CBL). All these cells, s everal kinds were in a mixed distribution, but usually one kind was predominant. IMALToma was divided into following subtypes:
      ① CCL subtype seen in 11 cases. The tumor cells were medium and small in size, with less cytoplasm, irregular and angular nuclei of dark staining, which looked like centrocytes.
      ② MCB subtype seen in 4 cases. The tumor cells were of medium size, their cytoplasm was abundant, lightly stained and clear. The nuclei were round, with visible nuclear membrane, fine chromatin and small nucleoli.
      ③ LPC subtype seen in 2 cases. The cytoplasm tumor cells looked like plasma cells and nuclei like small lymphocytes. The cytoplasm was abundant and stained red , in some, the cytoplasm contained immunoglobulin inclusions. The nuclei of tumo r cells were round, dark stained, similar to small lymphocyte.
      ④ CBL subtype: CBL cells were more than 50% in four cases, medium size with light stained cy toplasm and round vacuolated nuclei, and 1-3 basophilic nucleoli nearby the nucl ear membrane. CBL cells were focally distributed with a few CCL cells scattering or clustering around the CBL cells. Transition could be shown between CBL and CCL cells. Mitoses were easily found, especially the pathologic mitoses.

Figure 1 In IMALToma CCL cell infiltrated and destro yed glands forming the lymphoepithial lesion, HE stains. ×100
Figure 2 In LP, mantle cells increased in layers and infiltrated into germinal centers, dendritic cells and the macrophages with chr omophilic bodies were replayed entirely.
Figure 3 In IMALToma, lymphoplasmatic cells infilt rated mucosa membrane, in which the CD₂₀ was positive, ABC method. ×100

      In the above 3 subtypes, 14 with few or none of CBL cells were low-grade malignant. Another 2 of CCL type and 1 MCB type was low-grade malignant but with high-grade malignant component, of which the proportion of CBL cells was more t han 25%. Four CBL types having more than 50% CBL cells were highly malignant. Lymph node metastases were seen in 3 of 14 cases of low grade malignancy, 2 low grade malignancy with high-grade malignant component and 4 high grade malignant IMALToma.
      Four cases of LP were located at terminal ileum within the range of 20cm-40cm. They were hundreds stalkless polyps, varied from millet to broad bea n. Three-fourth were mushroom-like or narrow masses, which were 1cm× 1cm×1cm-6cm×4cm×2.5cm in size; with ulceration on the surface. Histologically, the lymph follicles were surrounded by numerous layers of lymphomatous lymphocytes, infiltrating into the germinal centers. The dendri tic cells and macrophages with chromophilic bodies decreased and even disappeare d. Neoplastic cells infiltrated diffusely, forming nodular and mantle-like grow th pattern. The nuclei of the lymphomatous cells were round or irregularly angul ar with thick nuclear membrane and condensed chromatin(Figure 2). One case showed blast cell transformation.

RESULT
Immunohistochemically, twenty one cases of IMALToma and four cases of LP were CD ₄₅ and CD₂₀ positive(Figure 3). The reactive lymph follicles we re polyclonal, while LEL and FC were monoclonal; one case of CBL lymphoma was negative for bcl-2. Ten cases and 5 cases were positive in CD₆₈ and CD_45R0, in reactive histocytes and small lymphocytes, respectively.

DISCUSSION
The significance of the LEL and FC pathological diagnosis of IMALToma.
      LEL is considered a characteristic feature of IMALToma^［1］. In our data, less than 50% (9/21) had LEL. The nest formation could also be found in the in flammatory and reactive status, it might be difficult to distinguish them from t he real LEL, in such case, immunohistochemistry may be helpful. The former is se veral leukocytes with poly-clone and the latter is the lymphocytes with mono -clone. FC, appeared in 9 cases, is easy to misjudge as reactive follicles.The following morphological characteristics and immuno-phenotype may be helpful for the differentiation: ① FC has no dendritic cells or macrophages with chrom ophilic bodies. ② CCL cell is the immunophenotype of B cells in the marginal ar ea, rather than at the germinal center^［2］.
      Both LEL and FC were characteristic features for diagnosis^［3］, but they could only be seen in some of the cases, then, immunohistochemistry and molecular biology technique should be done.

The diagnostic criteria and correlations of clinico-pathologic feature s of low and high-grade malignant IMALToma
Fourteen were of low-grade malignancy, including CCL, MCB and LPC subtypes. The proportion of CBL cells was more than 25% in two CCL lymphoma and one MCB lymph oma, one should pay attention to transformation from low-to high-grade malign ancy. Four CBL lymphomas were of high-grade malignancy, in which the CBL cells were ＞50%, distributing around the FC in fused clusters or trabeculae, and Ig might be positive and bcl-2 negative^［4,5］. The rates of metastasis of the above three types of lymphoma were 28.5%, 66.7% and 100%, respectively, which proved that histological grading and the clinical staging were intimately related to prognosis.

The origination of LP
The lymphomatous polyps were first described, and named LP by Corn in 196 1. The origination of LP was argued for a long time. Only recently, LP could be defined as originating from both mantle cells and the centrocytes, which were similar in morphology^［6］. The former was positive in IgD, CD₅ and cycl in D₁ without blastocyte transformation, while the latter was positive in IgM and CD₁₀ with blastocyte transformation^［7,8］. In our group, three cases had th e morphologic feature of mantle cells, one was originated from germinal center, which was transformed from centrocytes to centroblastocytes. Thus the term LP co uld not reflect the origination and the nature. LP has two patterns, showing sim ilar macroscopic and histologic features here we suggest a better terms for LP: mucosal mantle cell lymphoma and mucosal follicular lymphoma.

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