GASTROINTESTINAL LYMPHOMA

Any segment of the gastrointestinal tract may be secondarily involved by systemic dissemination of non-Hodgkin lymphomas. However, up to 40% of lymphomas arise in sites other than

lymph nodes, and the gut is the most common location. Conversely, about 1% to 4% of all gastrointestinal malignancies are lymphomas. By definition, primary gastrointestinal lymphomas

exhibit no evidence of liver, spleen, mediastinal lymph node, or bone marrow involvement at the time of diagnosis—regional lymph node involvement may be present. Primary

gastrointestinal lymphomas usually arise as sporadic neoplasms but also occur more frequently in certain patient populations: (1) Chronic gastritis caused by H. pylori, (2) chronic

spruelike syndromes, (3) natives of the Mediterranean region, (4) congenital immunodeficiency states, (5) infection with human immunodeficiency virus, and (6) following organ

transplantation with immunosuppression.

Intestinal tract lymphomas can be classified into B-cell and T-cell lymphomas. The B-cell lymphoma can be subdivided into MALT lymphoma, immunoproliferative small-intestinal

disease (IPSID), and Burkitt lymphoma.

1. MALT lymphoma is a sporadic lymphoma, which arises from the B cells of MALT (mucosa-associated lymphoid tissue, described under gastric lymphoma). This type of lymphoma

is the most common form in the Western hemisphere. The biologic features of these lymphomas are different from node-based lymphomas in that (1) many behave as focal tumors

in their early stages and are amenable to surgical resection; (2) relapse may occur exclusively in the gastrointestinal tract; (3) genotypic changes are different than those observed in

nodal lymphomas: the t(11;18) translocation is relatively common in MALT lymphoma; and (4) the cells are usually CD5- and CD10-negative. This type of gastrointestinal

lymphoma usually affects adults, has no gender predilection, and may arise anywhere in the gut: stomach (55% to 60% of cases); small intestine (25% to 30%), proximal colon

(10% to 15%), and distal colon (up to 10%). The appendix and esophagus are only rarely involved.

The pathogenesis of these lymphomas is under intense scrutiny. The concept has been advanced that lymphomas of MALT origin arise in the setting of mucosal lymphoid

activation and that these lymphomas are the malignant counterparts of hypermutated, postgerminal-center memory B cells. As discussed earlier, Helicobacter-associated chronic

gastritis, in particular, has been proposed as a driving force for the development of gastric MALT lymphoma, the result of antigen-driven somatic mutation of

gastric lymphoid tissue. However, the etiologic factors for intestinal lymphoma are still unknown, although history of IBD appears to increase the risk.

2. IPSID is also referred to as Mediterranean lymphoma. It is an unusual intestinal B-cell lymphoma arising in patients with Mediterranean ancestry, having a background of chronic

diffuse mucosal plasmacytosis. The plasma cells synthesize an abnormal Iga heavy chain, in which the variable portion has been deleted. A high proportion of patients have

malabsorption and weight loss preceding the development of the lymphoma. The diagnosis is made most commonly in children and young adults, and both sexes appear to be

affected equally. The exact etiology of this type of lymphoma is not known, although infection appears to play a role.[95]

3. The intestinal T-cell lymphoma is usually associated with a long-standing malabsorption syndrome (such as celiac disease) that may not constitute a true gluten-sensitive

enteropathy. This lymphoma occurs in relatively young individuals (age 30 to 40), often following a 10- to 20-year history of symptomatic malabsorption. Alternatively, a diffuse

enteropathy with malabsorption may accompany the development of a lymphoma. Intestinal T-cell lymphoma arises most often in the proximal small bowel, and its overall

prognosis is poor (reported 11% five-year survival rate).

Morphology.

Gastrointestinal lymphomas can assume a variety of gross appearances. Since all the gut lymphoid tissue is mucosal and submucosal, early lesions appear as plaque-like expansions of the

mucosa and submucosa. Diffusely infiltrating lesions may produce full-thickness mural thickening, with effacement of the overlying mucosal folds and focal ulceration. Others may be

polypoid, protruding into the lumen, or form large, fungating, ulcerated masses. Tumor infiltration into the muscularis propria splays the muscle fibers, gradually destroying them. Because

of this feature, advanced lesions frequently cause motility problems with secondary obstruction. Large tumors sometimes perforate because of lack of stromal support; reduction in tumor

bulk during chemotherapy also may lead to perforation.

In the earliest histologic lesions, atypical lymphoid cells may be seen infiltrating the mucosa, with effacement and loss of glands and massive expansion of lymphoid tissue. Extreme

numbers of atypical lymphoid cells may populate the superficial or glandular epithelium (lymphoepithelial lesion). With established lymphomas, the mucosa, submucosa, and even muscle

wall are replaced by a monotonous infiltrate of malignant cells, consisting of a mixture of small lymphocytes and immunoblasts in varying proportions. Lymphoid follicles are occasionally

formed. Most gut lymphomas are of B-cell type (over 95%) and are evenly split between low- and high-grade tumors. The small fraction of T-cell lymphomas occurring in the intestine are

commonly high-grade lesions.

Clinical Features.

With the exception of T-cell lymphomas, primary gastrointestinal lymphomas generally have a better prognosis than do those arising in other sites. Ten-year survival for patients with

localized mucosal or submucosal disease approaches 85%. Early discovery is key to survival; thus, gastric lymphomas generally have a better outcome than those of the small or large

bowel. In general, the depth of local invasion, size of the tumor, the histologic grade of the tumor, and extension into adjacent viscera are important determinants of prognosis.

MESENCHYMAL TUMORS

Mesenchymal tumors may occur anywhere in the alimentary tract. The nomenclature for these tumors is largely based on the tumor cell phenotypes. Lipomas show a propensity for the

submucosa of the small and large intestines, and lipomatous hypertrophy may occur in the ileocecal valve. A variety of spindle-cell lesions may arise in the muscle wall of any gut segment.

The great majority of these tumors are of smooth muscle origin, and hence can be termed leiomyomas and leiomyosarcomas. Gastrointestinal stromal tumors (GISTs), are now considered

to be a distinctive tumor type, characterized by c-KIT immunoreactivity, as discussed earlier (see "Gastric Tumors"). The small intestine is the second most common location for this

tumor, (the stomach being the most common). Both benign and malignant versions of GIST may occur at any age and in either sex. Vascular tumors such as Kaposi sarcomas are

considered elsewhere (see Chapter 11 ).

Morphology.

Lipomas are usually well-demarcated, firm nodules (almost always less than 4 cm in diameter) arising within the submucosa or muscularis propria. The overlying mucosa is stretched and

attenuated. Rarely, they grow to larger size and produce hemispheric elevation of the mucosa with ulceration over the dome of the tumor. Malignant stromal tumors (primarily

leiomyosarcoma) tend to produce large, bulky, intramural masses that eventually fungate and ulcerate into the lumen or project subserosally into the abdominal space. Histologically,

lipomas, leiomyomas, and leiomyosarcomas resemble their counterparts encountered elsewhere ( Chapter 26 ). In the case of the stromal tumors (e.g., leiomyomas and leiomyosarcomas),

large size and a high mitotic rate are correlated with an aggressive course.

Clinical Features.

Most mesenchymal tumors are asymptomatic. In the stomach, larger lesions (benign or malignant) may produce symptoms resembling those of peptic ulcer, particularly bleeding that is

sometimes massive. Intestinal lesions may present with bleeding, and for the small intestine, rare obstruction or intussusception. Benign lesions are easily resectable. Surgical removal is

usually possible for the malignant lesions as well, since they tend to grow as cohesive masses. Five-year survival rate for leiomyosarcoma, for example, is 50% to 60%. Metastases,

however, are present in about one third of cases.

Date: 2016-04-22; view: 1016